<SEC-DOCUMENT>0000874015-24-000116.txt : 20240221
<SEC-HEADER>0000874015-24-000116.hdr.sgml : 20240221
<ACCEPTANCE-DATETIME>20240221163827
ACCESSION NUMBER:		0000874015-24-000116
CONFORMED SUBMISSION TYPE:	10-K
PUBLIC DOCUMENT COUNT:		121
CONFORMED PERIOD OF REPORT:	20231231
FILED AS OF DATE:		20240221
DATE AS OF CHANGE:		20240221

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			IONIS PHARMACEUTICALS INC
		CENTRAL INDEX KEY:			0000874015
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		ORGANIZATION NAME:           	03 Life Sciences
		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:		24660339

	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 12-31-2023
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<div>UNITED STATES</div>
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  <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_abc08edcd1fe43ea9d3c681a610df170" contextRef="c20230101to20231231">10-K</ix:nonNumeric></div>

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    <td style="width: 36pt; vertical-align: top; font-family: 'Segoe UI Symbol'; font-size: 10pt;"><ix:nonNumeric name="dei:DocumentAnnualReport" id="Fact_3389ae58a27c4c25abe8002e78a8baec" contextRef="c20230101to20231231" format="ixt-sec:boolballotbox">&#9746;</ix:nonNumeric></td>

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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; font-weight: bold;">For the fiscal year ended <ix:nonNumeric name="dei:DocumentPeriodEndDate" id="Fact_ba92edc26fb2439c89f4179cb0357e70" contextRef="c20230101to20231231" format="ixt:date-monthname-day-year-en">December 31, 2023</ix:nonNumeric></div>

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    <td style="width: 36pt; vertical-align: top; font-family: 'Segoe UI Symbol'; font-size: 10pt;"><ix:nonNumeric name="dei:DocumentTransitionReport" id="Fact_dbe417a6b0814989bf3e65ad15d5efe7" contextRef="c20230101to20231231" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></td>

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          <div style="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;">TRANSITION&#160;REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES
              EXCHANGE ACT OF 1934</span></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; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Commission file number <ix:nonNumeric name="dei:EntityFileNumber" id="Fact_2a02cc327596498c9ffefe7299e0c2be" contextRef="c20230101to20231231">000-19125</ix:nonNumeric></div>

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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;"><ix:nonNumeric name="dei:EntityRegistrantName" id="Fact_b88ecd67e0734982a3bdce61652e451e" contextRef="c20230101to20231231">Ionis Pharmaceuticals, Inc</ix:nonNumeric>.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Exact name of Registrant as specified in its charter)</div>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="dei:EntityIncorporationStateCountryCode" id="Fact_f5da20d93cdd406d80b0a5c062fb1a8a" contextRef="c20230101to20231231" format="ixt-sec:stateprovnameen">Delaware</ix:nonNumeric></div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="dei:EntityTaxIdentificationNumber" id="Fact_594a5f4316a64081b9019bad44a42f6b" contextRef="c20230101to20231231">33-0336973</ix:nonNumeric></div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(State or other jurisdiction of incorporation or organization)</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(IRS Employer Identification No.)</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="dei:EntityAddressAddressLine1" id="Fact_211c1b4095834ef3981f9113c86cdc72" contextRef="c20230101to20231231">2855 Gazelle Court</ix:nonNumeric>, <ix:nonNumeric name="dei:EntityAddressCityOrTown" id="Fact_94522d7ac450466f86c13d8070ea089b" contextRef="c20230101to20231231">Carlsbad</ix:nonNumeric>, <ix:nonNumeric name="dei:EntityAddressStateOrProvince" id="Fact_c48bfd9da68f4151820fa685038cb67b" contextRef="c20230101to20231231">CA</ix:nonNumeric></div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="dei:EntityAddressPostalZipCode" id="Fact_f890b7588bca4d74bddcb94b934f17fc" contextRef="c20230101to20231231">92010</ix:nonNumeric></div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Address of Principal Executive Offices)</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Zip Code)</div>
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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="dei:CityAreaCode" id="Fact_8822686e982f41d7b77f7654283c3e72" contextRef="c20230101to20231231">760</ix:nonNumeric>-<ix:nonNumeric name="dei:LocalPhoneNumber" id="Fact_4a303ae4208f40c6a76139c34d547489" contextRef="c20230101to20231231">931-9200</ix:nonNumeric></div>

  <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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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Title of each class</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Trading symbol</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Name of each exchange on which registered</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:Security12bTitle" id="Fact_f5215697ae4e4384a3a6da0f4f7e6224" contextRef="c20230101to20231231">Common Stock, $.001 Par Value</ix:nonNumeric></div>
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          <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;">&#8220;</span><ix:nonNumeric name="dei:TradingSymbol" id="Fact_dc1c40fd36f9408ba739bb51576f19b5" contextRef="c20230101to20231231">IONS</ix:nonNumeric><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8221;</span></div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:SecurityExchangeName" id="Fact_d1fd3c668d4343118305222e620b02b5" contextRef="c20230101to20231231" format="ixt-sec:exchnameen">The Nasdaq Stock Market LLC</ix:nonNumeric></div>
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  <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>

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  <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_228b223f18934caf889ed7a237182c9a" contextRef="c20230101to20231231">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>

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  <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_d68786ee3af24b8584891985017e2a18" contextRef="c20230101to20231231">No</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;</span></div>

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  <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_0f457c595d024789b173b6a7c2c3be47" contextRef="c20230101to20231231">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>

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  <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_97f30237482c4c36965eae0f7aa3486d" contextRef="c20230101to20231231">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>

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  <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>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:EntityFilerCategory" id="Fact_5f8aa979b6f64c039a82b3e7cb2d4f38" contextRef="c20230101to20231231">Large Accelerated Filer</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;</span></div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accelerated Filer <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>
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          <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>
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          <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_4c1b67de436846ab8dfed39f5b73e5d6" contextRef="c20230101to20231231" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></span></div>
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          <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_80b2a313f5c74e829d784df597274c6a" contextRef="c20230101to20231231" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></span></div>
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  <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 Exchange Act. </span><span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

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  <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 404(b) 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_b207d0bfd2a34e75921e869fbe8f174d" contextRef="c20230101to20231231" format="ixt-sec:boolballotbox">&#9746;</ix:nonNumeric></span></div>

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  <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';"><ix:nonNumeric name="dei:DocumentFinStmtErrorCorrectionFlag" id="Fact_1a89dea036934e9c8cb40ac16e578bbe" contextRef="c20230101to20231231" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></span></div>

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  <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>

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  <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_34f5c68f749a4e67a42687c2da6a824f" contextRef="c20230101to20231231" format="ixt-sec:boolballotbox">&#9744;</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>

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  <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_df1689b2b0eb492596ad97b61dcbe15a" contextRef="c20230630" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">4,243,321,410</ix:nonFraction> as of June 30, 2023.*</div>

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  <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 15, 2024 was <ix:nonFraction name="dei:EntityCommonStockSharesOutstanding" id="Fact_bb4b7452577a4bac9c8e23744f9446f3" contextRef="c20240215" unitRef="U002" decimals="INF" scale="0" format="ixt:num-dot-decimal">145,751,797</ix:nonFraction>.</div>

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  <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>

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  <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 25, 2024 with the Securities and Exchange Commission in connection with
    the Registrant&#8217;s annual meeting of stockholders to be held on June 6, 2024 are incorporated by reference into Part III of this Report.</div>

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    <td style="width: 92.08%; vertical-align: top;">&#160;</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;">Excludes 39,747,443 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, 2023. 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>

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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;">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 our commercial medicines, additional medicines in development and technologies. 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. Except as required by law, we
    undertake no obligation to update any forward-looking statements for any reason. 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;"><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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our 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;">


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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: 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>

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</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: 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;">


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

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

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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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The impacts of pandemics, climate change, wars and other global events.</div>
        </td>

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  <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;">&#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.</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 practicable after we file such materials with, or furnish such materials to, 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, and other information 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, 2023</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>
        </td>

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

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

  </tr>

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    <td style="width: 10.51%; vertical-align: top;">&#160;</td>

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

    <td style="width: 6.27%; 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;">Page</div>
        </td>

  </tr>

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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 1.</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="#Item1">Business</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
        </td>

  </tr>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 1A.</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="#Item1A">Risk Factors</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;">49</div>
        </td>

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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 1B.</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="#Item1B">Unresolved Staff Comments</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;">65</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 1C.</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="#Item1C">Cybersecurity</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;">65</div>
        </td>

  </tr>

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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 2.</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="#Item2">Properties</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;">67</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 3.</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="#Item3">Legal Proceedings</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;">67</div>
        </td>

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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 4.</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="#Item4">Mine Safety Disclosures</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;">67</div>
        </td>

  </tr>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

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

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

  </tr>

  <tr>

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

    <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>

  </tr>

  <tr>

    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

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

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

  </tr>

  <tr>

    <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 5.</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="#Item5">Market for Registrant&#8217;s Common Equity, Related Stockholder
              Matters and Issuer Purchases of Equity Securities</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;">68</div>
        </td>

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  <tr>

    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 6.</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="#Item6">Reserved</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;">69</div>
        </td>

  </tr>

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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 7.</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="#Item7">Management&#8217;s Discussion and Analysis of Financial Condition and
              Results of Operations</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;">69</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <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: #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="#Item7A">Quantitative and Qualitative Disclosures About Market Risk</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;">79</div>
        </td>

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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 8.</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="#Item8">Financial Statements and Supplementary Data</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;">79</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <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: #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="#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: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79</div>
        </td>

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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 9A.</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="#Item9A">Controls and Procedures</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;">80</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 9B.</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="#Item9B">Other Information</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;">82</div>
        </td>

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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 9C.</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="#Item9C">Disclosure Regarding Foreign Jurisdictions that Prevent
              Inspections</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;">82</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

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

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

  </tr>

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

    <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>

  </tr>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

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

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

  </tr>

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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 10.</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="#Item10">Directors, Executive Officers and Corporate Governance</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;">82</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 11.</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="#Item11">Executive Compensation</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;">82</div>
        </td>

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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 12.</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="#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: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">
          <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: #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="#Item13">Certain Relationships and Related Transactions, and Director
              Independence</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;">83</div>
        </td>

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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 14.</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="#Item14">Principal Accountant Fees and Services</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;">83</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

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

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

  </tr>

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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; 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: #CCEEFF;">&#160;</td>

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

  </tr>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

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

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

  </tr>

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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 15.</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="#Item15">Exhibits, Financial Statement Schedules</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;">83</div>
        </td>

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    <td style="width: 10.51%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

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

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

  </tr>

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

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</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;">91</div>
        </td>

  </tr>


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    </div>

  </div>

  <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 style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><!--PROfilePageNumberReset%Num%4%%%--></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;">For three decades as a pioneer in RNA-targeted medicines, we have focused on bringing better futures to people with serious diseases.
    Today, we continue to drive innovation in RNA therapies. A deep understanding of disease biology and an industry-leading drug discovery technology propels our work, coupled with a passion and urgency to deliver better futures for patients.</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 five marketed medicines to treat serious diseases: SPINRAZA (nusinersen), QALSODY (tofersen), WAINUA (eplontersen),
    TEGSEDI (inotersen) and WAYLIVRA (volanesorsen). We also have a rich innovative late- and mid-stage pipeline in neurology, cardiology and other areas of high patient need. We currently have nine medicines in Phase 3 development and multiple additional
    medicines in early and mid-stage development.</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 past year, we made important progress executing on
      our vision to bring next-level value to patients and all stakeholders. We achieved this progress by focusing on a clear vision to prioritize and expand the Ionis wholly owned pipeline, deliver Ionis medicines directly to patients and enhance our
      technology leadership, all underscored by continued financial strength and responsibility. The United States, or U.S., Food and Drug Administration, or FDA, approved two Ionis-discovered medicines, QALSODY and WAINUA. We delivered positive Phase 3
      data readouts for WAINUA, olezarsen and donidalorsen. Our Phase 3 pipeline expanded with study starts for bepirovirsen, IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and zilganersen and we
      reported five additional positive data readouts from our mid- and late-stage pipeline. Our recent achievements position us to continue to deliver a steady cadence of potentially transformational medicines to patients in need in the near and mid-term.
      We also advanced our go-to-market plans for our near-term commercial opportunities, WAINUA, olezarsen and donidalorsen. And we expanded and diversified our technology when we advanced our first cardiac myocyte targeting medicine and medicines using
      our </span>mesyl phosphoramidate, or<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> MsPA, backbone into preclinical development.</span></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 $788 million for 2023 and ending the year with a cash and short-term investment balance of $2.3 billion. Our multiple sources of revenue and capital structure enable us to continue investing in
    our commercial readiness efforts for multiple late-stage programs, our innovative pipeline and our technology. By continuing to focus on these priorities, we believe we are well positioned to drive future growth and to bring next-level value to
    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. Our partner, Biogen, is responsible for commercializing SPINRAZA worldwide. From inception through December 31, 2023,
      we have earned more than $2.1 billion in revenues from our SPINRAZA collaboration, including more than $1.6 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;">QALSODY is an antisense medicine that received accelerated approval in April 2023 from the FDA for the treatment of adult patients with
      superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS, a rare, neurodegenerative disorder that causes progressive loss of motor neurons leading to death. Our partner, Biogen, is responsible for commercializing QALSODY worldwide. The
      European Medicines Agency, or EMA, is currently reviewing QALSODY for approval in the European Union, or EU.</div>

    <div><br/>
    </div>

    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA is a once monthly, self-administered subcutaneous LIgand-Conjugated Antisense, or LICA, medicine that received FDA approval in
      December 2023 for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis, or ATTRv-PN, a debilitating, progressive, and fatal disease. WAINUA is the only approved medicine for the treatment of ATTRv-PN that can
      be self-administered via an auto-injector. We and AstraZeneca are commercializing WAINUA in the U.S. with the launch having commenced in January 2024. We and AstraZeneca are seeking regulatory approval for WAINUA in Europe and other parts of the
      world. AstraZeneca has exclusive rights to commercialize WAINUA outside of the U.S.</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 sell TEGSEDI in the U.S. and Canada (collectively, North America) and Europe through our distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. In October 2023, our agreement for TEGSEDI in North America was
      terminated. As a result, Sobi is transitioning responsibilities to us. In February 2024, we began the process to withdraw the TEGSEDI New Drug Application, or NDA. 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>

  </div>

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    </div>

  </div>

  <div><br/>
  </div>

  <div>
    <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 approved in Europe and Brazil as an adjunct to diet in adult
      patients with genetically confirmed familial chylomicronemia syndrome, or FCS, and at high risk for pancreatitis. We sell 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><br/>
    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Medicines in Registration and Phase 3 Studies</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 nine medicines in registration or Phase 3 studies for eleven indications, which are:</div>

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA (eplontersen) is our medicine to treat patients with transthyretin amyloidosis, or ATTR, that is approved in the U.S. for the
    treatment of adults with ATTRv-PN, under regulatory review in other countries for ATTRv-PN and in development for ATTR cardiomyopathy, or ATTR-CM. In September 2023, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">The Journal of the American Medical Association</span>, or<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"> JAMA</span>, published positive results from the Phase 3 NEURO-TTRansform
    study in patients with ATTRv-PN showing WAINUA halted disease progression and continuously improved quality of life at 35-, 66- and 85-week analyses. In July 2023, we completed enrollment of the Phase 3 CARDIO-TTRansform study of WAINUA in patients
    with ATTR-CM with data planned for as early as 2025. In February 2024, the FDA granted Fast Track designation to WAINUA for the treatment of patients with ATTR-CM. Additionally, in January 2022 and October 2023, the FDA and EMA, respectively, granted
    orphan drug designation to WAINUA for the treatment of ATTR.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olezarsen is our medicine in development for FCS, an ultra-rare indication and severe hypertriglyceridemia, or SHTG, a much broader
    indication. In September 2023, we reported positive results from the Phase 3 Balance study in patients with FCS showing statistically significant triglyceride lowering and a substantial reduction in acute pancreatitis events in addition to a favorable
    safety and tolerability profile<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Based on our positive Phase 3 results in FCS patients we are preparing regulatory submissions to the FDA and EMA. </span>In January 2023, the
    FDA granted fast track designation to olezarsen for the treatment of patients with FCS.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Additionally, we are currently conducting a broad Phase 3 development program for
      olezarsen for the treatment of SHTG including three Phase 3 studies supporting development (CORE, CORE2 and ESSENCE). In February 2024, the FDA granted Breakthrough Therapy designation and orphan drug designation to olezarsen for the treatment of
      FCS.</span> Additionally, in January 2023, the FDA granted olezarsen Fast Track designation for the treatment of patients with FCS.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Donidalorsen is our medicine in development for hereditary angioedema, or HAE.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>In January 2024, we reported positive data from the Phase 3 OASIS-HAE study in patients treated every four weeks or patients treated every eight weeks. We are currently conducting <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">OASIS-Plus, our </span>open-label study in patients who were either previously treated with other prophylactic therapies or who have completed OASIS-HAE<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>Throughout 2022 and 2023, we reported positive data from the Phase 2 study and Phase 2 open-label extension, or OLE<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>study,
    including two-year OLE data. In December 2023, we licensed European commercialization rights of donidalorsen to Otsuka Pharmaceutical Co., Ltd., or Otsuka. We are preparing to submit an NDA to the FDA. Otsuka is preparing to submit a Marketing
    Authorization Application, or MAA, to the EMA. In September 2023 and February 2024, the FDA and EMA, respectively, granted orphan drug designation to donidalorsen.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Zilganersen is our medicine in development for Alexander disease, or AxD<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In September 2023, we advanced zilganersen into the Phase 3 portion of its ongoing study for patients with AxD. In </span>September 2020 and October 2019, the FDA and EMA, respectively, granted orphan drug designation to
    zilganersen. Additionally in August 2020, the FDA granted rare pediatric designation to zilganersen.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ulefnersen is 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><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We are currently conducting a Phase 3 study of ulefnersen in juvenile
      and adult patients with FUS-ALS</span>. In August 2023 and September 2023, the FDA and EMA, respectively, granted orphan drug designation to ulefnersen.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">QALSODY (tofersen) is our medicine to treat patients with SOD1-ALS. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In April 2023, the FDA granted Biogen accelerated approval of QALSODY for patients with SOD1-ALS. </span>QALSODY is currently under regulatory review in the EU. Additionally, Biogen is developing QALSODY to treat presymptomatic SOD1-ALS
    patients in the ongoing ATLAS study. In September 2016 and August 2016, the FDA and EMA, respectively, granted orphan drug designation to QALSODY.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pelacarsen is our medicine in development to treat patients with elevated lipoprotein(a), or Lp(a)-driven cardiovascular disease, or CVD.
    <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Novartis is developing pelacarsen, including conducting the ongoing Lp(a) HORIZON Phase 3 cardiovascular outcome study in patients with elevated Lp(a)-driven CVD, which
      achieved full enrollment in July 2022 with more than 8,000 patients. In April 2020, </span>the FDA granted Fast Track 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;">Bepirovirsen is our medicine in development for chronic hepatitis B virus, or HBV<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. GSK is developing bepirovirsen, including conducting the ongoing B-Well Phase 3 program in patients with HBV. GSK reported positive results from Phase 2 studies in 2023, including durable response data from the Phase 2 B-Sure
      long-term follow-up study of bepirovirsen in complete responder patients from the Phase 2b B-Clear study of patients with HBV. In February 2024, the FDA granted Fast Track designation to bepirovirsen.</span></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">IONIS-FB-L<sub>Rx</sub> is our medicine in development for immunoglobulin A, or IgA, nephropathy, or IgAN, and geographic atrophy, or GA.
    <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the second quarter of 2023, Roche advanced IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> into Phase 3
      development in patients with IgAN. In October 2023, we reported positive interim data from the ongoing Phase 2 study of IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in patients with IgAN.
      Additionally, IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> is in an ongoing Phase 2 study in patients with GA, refer to the IONIS-FB-L</span><sub>Rx </sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">description below for further details.</span></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;">Our Marketed Medicines &#8211;Bringing Value to Patients Today</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;">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;">SMA </span>in pediatric and adult patients.</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;">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>

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  <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, in untreated people 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% of the SMN protein critical for motor neurons, resulting in severe and progressive loss of motor function and strength.</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 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>

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  <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: 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, or CSF, 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: 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 2023, Biogen presented interim results from the RESPOND study that showed improved motor function in most participants treated with SPINRAZA following treatment with onasemnogene abeparvovec.</div>
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            <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 with risdiplam.</div>
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  <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 OLE study for patients with SMA who participated in prior SPINRAZA studies.</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;">QALSODY &#8211; </span>QALSODY (tofersen) is
      an antisense medicine used to treat ALS in adults who have a mutation in the superoxide dismutase 1, or SOD1, gene, or SOD1-ALS. The FDA granted QALSODY accelerated approval based on reduction in plasma neurofilament light chain, or NfL, observed in
      patients treated with QALSODY. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).</div>

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    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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. </span>It is estimated that there are approximately 1,400 patients with SOD1-ALS in the 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: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen is also evaluating QALSODY for treatment of <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">presymptomatic








        individuals who have a SOD1 genetic mutation</span>. See the &#8220;Tofersen&#8221; description under &#8220;Our Phase 3 Pipeline&#8221; section below for further information on the development program for presymptomatic individuals. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Tofersen is one of three medicines we have in development to treat ALS.</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;">QALSODY received accelerated approval from the U.S. FDA in April 2023 and is currently under regulatory review in the EU. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The QALSODY 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 the Phase 3 VALOR study and the Phase 3 OLE study. The 12-month integrated data show that earlier initiation of QALSODY, 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 QALSODY (at the start of VALOR) to those who had a delayed
      initiation of QALSODY (six months later, in the OLE).</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 time of the 12-month analysis, because the majority of participants survived without permanent ventilation, the median time to
    death or permanent ventilation, could not be estimated. However, early survival data suggest a lower risk of death or permanent ventilation with earlier initiation of QALSODY. 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. QALSODY reduced total 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 QALSODY, 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;">QALSODY had a favorable safety and tolerability profile.</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 FDA and EMA granted QALSODY orphan drug designation for the treatment of ALS in September 2016 and August 2016, 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;">In December 2018, Biogen exercised its option to license QALSODY. As a result, Biogen is responsible for global development, regulatory
    and commercialization activities, and costs for QALSODY.</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;">WAINUA &#8211; </span>WAINUA (eplontersen) <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">injection is a LICA medicine indicated for the treatment of adults with ATTRv-PN. WAINUA prevents the production of TTR protein, reducing the amount of amyloid buildup that
      damages organs and tissues. WAINUA was approved by the FDA in December 2023.</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;">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>

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    <div style="text-align: justify; text-indent: 36pt; 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 with ATTRv-PN and those with ATTRv- mixed phenotype worldwide.</div>

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    <div style="text-align: justify; text-indent: 36pt; 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 a variety of symptoms, including progressive difficulty with motor functions. As a result, we are developing WAINUA to treat all types of ATTR. See the
      &#8220;WAINUA&#8221; description under &#8220;Our Phase 3 Pipeline&#8221; section below for further information on our development program for ATTR-CM.</div>

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    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">FDA approval was based on the interim analysis of the Phase 3 NEURO-TTRansform study in patients with ATTRv-PN. NEURO-TTRansform was <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 WAINUA. The study compared WAINUA to the historical placebo
        arm from the TEGSEDI (inotersen) NEURO-TTR Phase 3 study. </span>In the interim analysis, WAINUA 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, WAINUA achieved an 81% (p&lt;0.0001) least squares, or LS, mean reduction in the co-primary endpoint of serum TTR concentration compared to baseline, demonstrating reduced TTR protein production.
      WAINUA 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 WAINUA
      significantly improved patient-reported quality of life compared to the external placebo group (p&lt;0.0001). In September 2023, The <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Journal of American
        Medical Association, or JAMA,</span> published the Phase 3 NEURO-TTRansform study results.</div>

    <div><br/>
    </div>

    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, in April 2023, we presented positive data that WAINUA met all co-primary and secondary endpoints in the NEURO-TTRansform
      study at the final analysis at week 66. At week 66:</div>

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    <td style="width: auto; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA achieved a LS mean reduction of 82% in serum TTR concentration from baseline, compared to an 11% reduction from baseline in the external
              placebo group (p&lt;0.0001).</div>
          </td>

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            <div style="text-align: left; margin-left: 36pt; 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;">WAINUA stopped disease progression as measured by mNIS+7 resulting in a 0.28 point LS mean increase compared to a 25.06 point increase for the
              external placebo group from baseline (24.8 point LS mean improvement; p&lt;0.0001).</div>
          </td>

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          </td>

    <td style="width: auto; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA improved quality of life demonstrating a 5.5 point LS mean decrease (improvement) on the Norfolk QoL-DN, compared to a 14.2 point increase
              (worsening) in the external placebo group (19.7 point LS mean improvement; p&lt;0.0001).</div>
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    <div><br/>
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    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">And in July 2023, we reported that WAINUA continued to halt neuropathy disease progression and improve quality of life in patients with
      ATTRv-PN through the end of treatment analysis at week 85.</div>

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

    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA is currently under regulatory review in the EU and other countries for the treatment of patients with ATTRv-PN.</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 2022 and October 2023, the FDA and EMA, respectively, granted orphan drug designation to WAINUA for the treatment of ATTR.</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 WAINUA in the U.S. We initially
    granted AstraZeneca exclusive rights to commercialize WAINUA outside the U.S., except for certain Latin American countries. In July 2023, we expanded those rights to include Latin America.</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: 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. Refer to the
      section titled, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Overview</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for further details on 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>

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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; 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>

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  <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>

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  <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>

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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 Innovative Pipeline of Investigational Medicines</div>

  <div><br/>
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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As a pioneer in RNA-targeted therapeutics, we continue to drive innovation with a leading pipeline in neurology, cardiology and other
    areas of high patient need.</div>

  <div><br/>
  </div>

  <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 and includes the disease indication, the partner (if the medicine is
    partnered), and the development status of each medicine. We categorize first-in-patient studies to establish a medicine&#8217;s safety profile as Phase 1/2 and in the table below these are listed in the Phase 2 column. Studies in patients that are designed
    to establish an investigational medicine&#8217;s proof of concept and additional safety profile are also listed in Phase 2. Pivotal studies designed to enable registrational filing for marketing authorization are listed in Phase 3. 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="723" height="324" src="image01.jpg" alt="graphic"/></div>

  <div style="text-align: center;"><img width="718" height="81" src="image04.jpg" alt="graphic"/></div>

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  <div style="text-align: center; margin-left: 18pt;"><sup>1</sup><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;">Granted Otsuka exclusive rights to commercialize donidalorsen in Europe.</span></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;">Our Phase 3 Pipeline</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 have nine medicines in our Phase 3 pipeline:</div>

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  <div style="text-align: center;"><img width="725" height="356" src="image05.jpg" alt="graphic"/></div>

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  <div style="text-align: center; margin-left: 18pt;"><sup>1</sup><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;">Granted Otsuka exclusive rights to commercialize donidalorsen in Europe.</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-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 LICA medicine we designed </span>to inhibit the production of TTR protein. As discussed above under &#8220;WAINUA&#8221; in our &#8220;Marketed Medicines&#8221; section, we are developing eplontersen as
    a monthly self-administered subcutaneous injection to treat all types of ATTR, including ATTR-CM.</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;">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 a variety of symptoms, including progressive difficulty with motor functions.</div>

  </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;">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 primary endpoint in the CARDIO-TTRansform study is a composite outcome of cardiovascular mortality and recurrent cardiovascular clinical events up to Week 140.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>In July 2023, we announced that the CARDIO-TTRansform 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 January 2022 and October 2023, the FDA and EMA, respectively, granted orphan drug designation to WAINUA for the treatment of ATTR.</div>

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  <div><br/>
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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>

  <div><br/>
  </div>

  <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>

  <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;">In September 2023, we reported positive topline data from
      the Phase 3 Balance study in patients with FCS. The study met its primary efficacy endpoint with a statistically significant reduction in triglyceride (TG) levels with the olezarsen 80 mg monthly dose at six months compared to placebo (p=0.0009);
      triglyceride lowering continued to improve at 12 months. In addition, olezarsen 80 mg showed a substantial reduction in acute pancreatitis events compared to placebo, a key secondary endpoint. Treatment with olezarsen 80 mg resulted in a &gt;75%
      reduction in apoC-III, a protein produced in the liver that regulates TG metabolism in the blood. In addition to the 80 mg monthly dose, the study also evaluated a 50 mg monthly dose. Olezarsen demonstrated a dose-dependent effect, with both study
      doses showing a substantial reduction in acute pancreatitis compared to placebo. The 50 mg dose did not reach statistical significance at six months on the primary endpoint of triglyceride lowering (p=0.0775). Olezarsen demonstrated a favorable
      safety and tolerability profile in the study.</span><span style="background-color: #F1F1F1; font-size: 12pt; font-family: 'Times New Roman', Times, serif;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Based on
      the positive results, we plan to file a New Drug Application, or NDA, in 2024 with the U.S. FDA in addition to EU regulatory filings for patients with FCS.</span></div>

  <div><br/>
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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 conducting ongoing Phase 3 studies for the expanded SHTG patient population. 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 month six.</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;">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.
    Olezarsen also achieved statistical significance in numerous key secondary endpoints, including significant reductions in apoC-III. Olezarsen had a favorable safety and tolerability profile supportive of continued development.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In February 2024, the FDA granted <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Breakthrough Therapy
      designation and </span>orphan drug designation to olezarsen for the treatment of FCS. Additionally, in January 2023, the FDA granted olezarsen Fast Track designation for the treatment of patients with FCS.</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;">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 inhibit the production of prekallikrein, or PKK.
    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>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2024, we reported positive topline data from the Phase 3 OASIS-HAE study in patients with HAE. The study met its primary
    efficacy endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated with 80 mg of donidalorsen via subcutaneous injection dosed every four weeks, or Q4W, (p&lt;0.001) or every eight weeks, or Q8W, (p=0.004)
    compared to placebo. In addition, the trial showed donidalorsen achieved statistical significance on all secondary endpoints in the Q4W group and key secondary endpoints in the Q8W group. Donidalorsen demonstrated a favorable safety and tolerability
    profile in the study. Based on the positive results, we plan to file a NDA in 2024 with the U.S. FDA. Otsuka, which has exclusive rights to commercialize donidalorsen in Europe, is preparing to submit a Marketing Authorization Application to the
    European Medicines Agency, or EMA.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">In 2021 and 2022 we reported positive results from the Phase 2 clinical study of donidalorsen in patients with HAE. And in 2022 and
    2023, we presented positive results from the Phase 2 OLE study of donidalorsen in patients with HAE. Following the 13-week blinded, placebo-controlled Phase 2 study with a fixed 13-week dosing period where they received donidalorsen 80 mg every four
    weeks, patients were eligible for enrollment in the OLE study. Of the 20 Phase 2 study participants, 17 entered the OLE study and were on a fixed 13-week dosing period where they received 80 mg every four weeks. From week 17 through two years, patients
    entered a flexible dosing period where they either received donidalorsen 80 mg every four weeks, 80 mg every eight weeks, or 100 mg every four weeks.<span style="background-color: #F1F1F1; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>Over








    the two years, patients treated with donidalorsen via subcutaneous injection showed an overall sustained mean reduction in HAE attack rates of 96% from baseline, from 2.70 to 0.06 attacks per month, across all dosing groups. Furthermore, all patients
    treated with donidalorsen reported a clinically meaningful improvement in quality of life as measured by the Angioedema Quality of Life Questionnaire (AE-QoL) over two years. Donidalorsen had a favorable safety and tolerability profile in the study.</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 2023 and February 2024, the FDA and EMA granted orphan drug designation to donidalorsen.</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 2023, we granted Otsuka exclusive rights to commercialize donidalorsen in Europe.</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% 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: 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 we designed to inhibit the production of glial fibrillary acidic protein, or GFAP. We are developing zilganersen as a potential therapy for AxD, 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 and in September 2023, we advanced zilganersen into the
    Phase 3 portion of the pivotal study. The pivotal 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;">In </span>September 2020 and October 2019, the FDA and
    EMA, respectively, granted orphan drug designation to zilganersen. Additionally in August 2020, the FDA granted rare pediatric designation to zilganersen.</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;">Ulefnersen (FUS)</span> &#8211; Ulefnersen
    (formerly 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.</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 ulefnersen in patients with FUS-ALS. The Phase 3 trial of ulefnersen is a global,
    multi-center, randomized, double-blind, placebo-controlled study in approximately 75 patients designed to assess the efficacy, safety and tolerability of ulefnersen. Part 1 of the trial consists of patients randomized to receive a loading regimen of
    ulefnersen or placebo for days one, 28 and 85 after which patients are dosed quarterly for a total of 61 weeks, followed by a 12 week follow up for participants entering Part 2 or 40 week follow up for participants not entering Part 2. Part 2 is an
    open-label period in which all patients in the trial will receive ulefnersen 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 joint rank analysis
    of the combined assessment of 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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2023 and September 2023, the FDA and EMA, respectively, granted orphan drug designation to ulefnersen.</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;">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 SOD1 protein, which
      is a well understood genetic cause of ALS. As discussed above under the &#8220;QALSODY&#8221; section in our &#8220;Marketed Medicines&#8221; section, Biogen is also evaluating tofersen for treatment of <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">presymptomatic individuals who have a SOD1 genetic mutation</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 April 2021, Biogen initiated a 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: left; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2016 and August 2016, the FDA and EMA, respectively, granted orphan drug designation to tofersen.</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;">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 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 arms will be stratified based on HBsAg levels 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 positive 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. The end of study results showed that treatment with bepirovirsen in some patients 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 that was administered weekly at a dose of 300 mg per week for 24 weeks, with loading doses administered on day four and 11 (treatment arm 1), resulted
    in 9% of patients on NA treatment and 10% of patients not on NA treatment both achieving the primary outcome of HBsAg levels and HBV DNA levels below the LLOQ. This is defined as a sustained response and was observed for 24 weeks post last dose.
    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. Additionally in June 2023, GSK
    presented durable response data from the Phase 2 B-Sure long-term follow-up study of bepirovirsen in complete responder patients from the Phase 2b B-Clear study of patients with HBV. 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 October 2023, GSK reported data from the B-Together Phase 2b study of bepirovirsen in patients with chronic HBV infection at the
    AASLD Liver Meeting. The data showed that between 9-15% of patients attained the primary outcome of HBsAg and HBV DNA below the LLOQ for 24 weeks after planned end of sequential treatment with pegylated interferon, in the absence of newly initiated
    antiviral therapy. Additionally, all patients who achieved the primary endpoint had a baseline HBsAg &#8804;3000 IU/mL. 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: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In February 2024, the FDA granted bepirovirsen Fast Track designation for the treatment of patients with chronic HBV infection.</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;">IONIS-FB-L</span><sub style="font-weight: bold;">Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> (IgAN) </span>(RG6299)<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;"> IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 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 IgAN. </span>As discussed below under the &#8220;IONIS-FB-L<sub>Rx</sub>&#8221; section in our &#8220;Other Medicines in Development&#8221; section, we are also developing IONIS-FB-L<sub>Rx</sub> for <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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.</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 April 2023, Roche initiated a Phase 3 study of
      IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, called IMAGINATION, in patients with IgAN. IMAGINATION is a multi-center, randomized, double-blind, placebo-controlled study enrolling
      approximately 430 patients designed to assess the efficacy, safety and tolerability of IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>The primary endpoint is the change from
    baseline in the urine protein-to-creatinine ratio, or UPCR, at week 37.</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 open-label 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. Additionally, in November 2023 at ASN Kidney Week, we presented new positive interim results
    from the ongoing Phase 2 study, which included results from 13 patients. The results showed that IONIS-FB-L<sub>Rx</sub> effectively and selectively reduced circulating FB, Alternate Pathway Activity, or AH50 and urinary complement Ba. Additionally,
    IONIS-FB-L<sub>Rx</sub> reduced established proteinuria in patients with IgAN after six-months of treatment. The Phase 2 open-label study remains ongoing and will evaluate IONIS-FB-L<sub>Rx</sub> in approximately 25 patients with IgAN. IONIS-FB-L<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 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: 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;">We have a leading neurology franchise that includes three approved medicines for serious neurological diseases and a pipeline of
    investigational potential disease-modifying treatments for a broad range of neurological diseases. As we look to expand our wholly owned pipeline, we are focused on four pillars within our neurology franchise. We are first focusing on two areas: rare
    pediatric neurology and dementia, with plans to move into neuromuscular and peripheral neuropathies and motor diseases and then common neurological diseases in the future. We recently added ION717 for prion disease to our pipeline with plans to add
    three additional medicines by the end of 2024.</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; See the medicine
    description under &#8220;Our Phase 3 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;">Ulefnersen</span> &#8211; See the medicine
    description under &#8220;Our Phase 3 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 Phase 3 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;">ION717 (PRNP)</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;">&#8211; </span>ION717 is an investigational antisense medicine we designed to
    inhibit the production of prion protein, or PrP, for the potential treatment of prion disease. Prion disease is a rare, fatal neurodegenerative disease caused by misfolding of PrP which accumulates in the brain. People with prion disease often
    experience progressive memory impairment, personality changes, difficulties with movement and loss of independence. There are currently no effective disease-modifying treatments for prion disease. In most cases, a person succumbs to prion disease
    within a year following symptom onset.</div>

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  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2023, we initiated the Phase 1/2, PrProfile, study of ION717 in patients with prion disease. The current study is a
    randomized, multi-center, double-blind, placebo-controlled study in approximately 55 patients designed to assess the safety, tolerability and pharmacokinetics of multiple dose levels of ION717 administered intrathecally.</div>

  <div style="text-align: justify; text-indent: 35.3pt;"><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;">IONIS-MAPT</span><sub style="font-weight: bold;">Rx</sub>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(TAU) </span>(BIIB080) &#8211; IONIS-MAPT<sub>Rx</sub> is an investigational antisense medicine we designed to selectively
    inhibit production of the microtubule-associated protein tau (MAPT), or tau protein in the brain. We are developing IONIS-MAPT<sub>Rx</sub> to treat people with Alzheimer&#8217;s disease, or AD.</div>

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  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AD is characterized predominantly by memory impairment and behavioral changes, resulting in a person&#8217;s inability to independently perform
    daily activities. AD generally occurs late in life and may progress to death in five to 20 years after the onset of the 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;">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 March 2023,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Biogen presented ne</span>w data from the
    Phase 1/2 study at the International Conference on Alzheimer's and Parkinson's Diseases. The data showed <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that IONIS-MAPT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> reduced soluble tau protein in CSF in a dose-dependent and sustained manner in patients with early-stage AD. IONIS-MAPT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> also reduced aggregated tau pathology, as measured by positron emission tomography</span>, or <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">PET</span>,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in all brain composites assessed. In October 2023, these data were published in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">JAMA</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Additionally in October 2023, Biogen presented new data from the Phase 1/2 study at The Clinical Trials on Alzheimer&#8217;s Disease, or CTAD, conference. The data showed a numerical difference
      favoring IONIS-MAPT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on multiple cognitive and functional scales for the patients receiving higher doses of IONIS-MAPT</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> throughout the multiple ascending dose and long-term extension compared to matched external control patients receiving placebo. The assessments included: Clinical Dementia Rating
      Sum of Boxes, or CDR-SB, Mini-Mental State Examination, or MMSE and, Functional Activities Questionnaire, or FAQ.</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 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 AD
    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 AD. The study demonstrated robust time and dose dependent lowering
    of tau protein in CSF 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>

  <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>

  <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 toxic aggregation of TDP-43, an RNA binding protein
    found in most patients with ALS, including the approximately 90% 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 antisense 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 50 patients designed to assess the safety, tolerability and activity of multiple ascending doses of ION582 administered intrathecally. In November 2023, we announced that the HALOS study had completed enrollment.</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 2023, we presented initial observations from the ongoing Phase 1/2 study at the Foundation for Angelman Syndrome, or FAST,
    summit. The data demonstrated that approximately 70% of patients showed a reduction in slow-wave electroencephalogram, or EEG, delta activity and over 80% showed an increase in faster frequency rhythms. Additionally, a majority of patients showed
    improvement in overall functioning on the SAS-CGI-C scale. A majority of patients also showed improvement on the total Bayley score, which is a direct assessment of clinical functioning.</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 May 2022 and June 2022, the FDA and EMA, respectively, granted orphan drug designation to ION582. Additionally in July 2022 and May
    2022, the FDA granted Fast Track designation and rare pediatric designation to ION582, 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;">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 2015 and March 2015, the FDA and EMA, respectively, granted orphan drug designation to tominersen. Additionally in August
    2018, the EMA granted PRIME designation to tominersen.</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;">Our cardiovascular franchise includes investigational medicines that target the major risk factors of CVD.</div>

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  <div style="text-align: center;"><img width="722" height="164" src="image08.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 Phase 3 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 Phase 3 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 Phase 3 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 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;">ION904 (AGT)</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In November 2023 at the AHA annual meeting we presented
      positive results from the 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. ION904 significantly reduced AGT levels compared to placebo.
      ION904 had a favorable safety and tolerability profile supportive of continued development.</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;">Other Medicines for High Patient Need 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 other medicines for high patient need in development that are outside of our cardiovascular and neurological franchises
    that we believe could represent compelling opportunities for us, including our Specialty Rare medicines, donidalorsen and sapablursen.</div>

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  <div style="text-align: center;"><img width="718" height="57" src="image09.jpg" alt="graphic"/><img width="719" height="80" src="image10.jpg" alt="graphic"/></div>

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    <div style="text-align: center; margin-left: 18pt;"><sup>1</sup><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;">Granted Otsuka exclusive rights to commercialize donidalorsen in Europe.</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;"> <br/>
    </span></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;">Donidalorsen</span> &#8211; See the medicine
    description under &#8220;Our Phase 3 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;">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>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">PV is a rare disease driven by a mutation in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">JAK2 </span>gene that is potentially fatal and characterized 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 and symptoms such as fatigue and impaired cognitive function. 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; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2020, the FDA granted Fast Track designation to sapablursen for polycythemia vera.</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;">Bepirovirsen</span> &#8211; <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">See the medicine description under &#8220;Our </span>Phase 3 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><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> (IgAN)</span> &#8211; <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">See the medicine
      description under &#8220;Our </span>Phase 3 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;">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;">(DGAT2)</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 CVD, 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% of the global population has NAFLD, 1.5% to 6.5% have NASH, and up to 10% 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; 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 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 IgAN (see section above &#8220;Our </span>Phase 3 Pipeline<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8221; for discussion of IgAN) and GA secondary to 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;">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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In June 2019, we initiated a Phase 2 GOLDEN 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 AMD. 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. In August 2023, we announced that the GOLDEN study had completed enrollment.</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 for IgAN.<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;">ION839 (PNPLA3)</span> &#8211; <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ION839 (AZD2693) is an investigational LICA medicine we designed to inhibit the production of patatin-like phospholipase domain-containing 3, or PNPLA3, protein. PNPLA3 is a
      protein that is found on the surface of intracellular lipid droplets. Studies have shown that a common genetic mutation of PNPLA3 is strongly associated with an increased risk for NASH. The mutant PNPLA3 protein is resistant to degradation, causing
      it to accumulate on the surface of lipid droplets, which disrupts the normal process for degrading lipid droplets, leading to increased liver fat accumulation, the underlying pathology of NASH.</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 March 2023, AstraZeneca initiated a Phase 2b study of ION839 in patients with <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">confirmed NASH with fibrosis and who are carriers of the PNPLA3 mutation. The Phase 2b study is </span>a multi-center, randomized, double-blind, placebo-controlled clinical study in approximately 180 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
      ION839. The primary endpoint is the proportion of patients achieving NASH resolution without worsening of fibrosis based on histology after 52 weeks of treatment.</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 April 2018, AstraZeneca exercised its option to license ION839.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> As a result, AstraZeneca is responsible for global development, regulatory and commercialization activities, and costs for ION839.</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 three decades through our innovations in science and technology, we have enhanced the profiles of RNA-targeted medicines and pursued
    new opportunities in emerging areas of genetic medicine.<span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">&#160;</span>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 have also added capabilities to utilize RNA interference, or RNAi, and potentially gene editing in addition to our novel antisense technology, which gives us the potential to deliver
    medicines to a greater number of people living with serious diseases.</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 Ionis&#8217; Technology</div>

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  </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 WAINUA, 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;">We also now use small interfering RNA (siRNA) technology, in addition to antisense technology, in the development of new medicines. Like
    antisense, siRNA medicines target RNA, and can decrease the production of specific proteins involved in disease. For each program we work on, we choose the approach which demonstrates the best potential product profile for the indication we are
    pursuing.</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 surface 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, including in our Phase 3 studies of WAINUA (for ATTRv-PN), olezarsen (for
    FCS patients) and donidalorsen (for 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; 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 Bicycle LICA technology, siRNA technology and MsPA backbone chemistry. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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. We
    currently have multiple new programs using our MsPA backbone, designed to improve both efficacy and durability, in 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;">Bicycle Collaboration</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 2021, we entered into a collaboration with Bicycle Therapeutics that we expect can expand our LICA platform to target both skeletal
    and cardiac muscle, and potentially deliver medicines across the blood brain barrier. Bicycles are small, bicyclic peptides that have high affinity and selectivity for protein targets. Our collaboration with Bicycle allows us to utilize Bicycles that
    bind transferrin receptor 1 to facilitate the tissue specific delivery of oligonucleotide drugs (both antisense and siRNAs). We advanced our first Bicycle LICA program into preclinical development in 2023.</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 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: 36pt; 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Collaborative Arrangements</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 have established alliances with a cadre of leading global pharmaceutical companies. Our partners include the following companies,
      among others: AstraZeneca, Biogen, GSK, Novartis, Otsuka 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 addition, we are eligible to receive 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 4, <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-style: italic; 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
    SMA. In April 2023, the FDA granted accelerated approval for QALSODY (tofersen) in the U.S. to treat patients with SOD1-ALS. Biogen developed QALSODY under our 2013 strategic neurology collaboration. In addition, we and Biogen are currently developing
    numerous other investigational medicines to treat neurodegenerative diseases, including medicines in development to treat people with ALS, SMA, AS, AD, and PD. From inception through December 31, 2023, we have generated more than $3.8 billion in payments from our Biogen collaborations.</div>

  <div>
    <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 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 </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recognized more than $2.0 billion in total revenue under our SPINRAZA
      collaboration, including more than $1.6 billion in revenue from SPINRAZA royalties and more than $425 million in R&amp;D revenue.</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;">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 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.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, Biogen exercised its option to license ION306. <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>We will receive development and regulatory milestone payments from
    Biogen if new medicines, including ION306, advance towards marketing approval.</div>

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    </div>

  </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 this collaboration, we are eligible to receive development, regulatory and sales milestone payments. 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, 2023, 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 2018, we and Biogen entered into a strategic collaboration to develop novel antisense medicines for a broad range of neurological
    diseases. We also entered into a Stock Purchase Agreement, or SPA. As a result, we received a payment related to the SPA in addition to an upfront payment at the commencement of this collaboration. 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. In most cases, Biogen will 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>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For each medicine under this collaboration, we are eligible to receive a license fee, development milestone payments and regulatory
    milestone payments. 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, 2023, 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 2013, we and Biogen entered into a 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. In
    most cases, we are 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 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.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are currently advancing four investigational medicines in development under this collaboration, including a medicine for Parkinson&#8217;s
    disease (ION859), two medicines for ALS (QALSODY and ION541) and a medicine for multiple system atrophy (ION464). In 2018, Biogen exercised its option to license QALSODY, our medicine that received accelerated approval in April 2023 from the FDA for
    the treatment of adult patients with SOD1-ALS. As a result, Biogen is responsible for global development, regulatory and commercialization activities and costs for QALSODY.</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 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 QALSODY, we are eligible to receive a license fee, development milestone payments and regulatory
    milestone payments. In addition, we are eligible to receive tiered royalties ranging from 11 percent to 15 percent on net sales of QALSODY.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For each of the other antisense molecules that are chosen for drug discovery and development under this collaboration, we are eligible to
    receive a license fee, development milestone payments and 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, 2023, we have generated more than $325 million in payments under our 2013 strategic
    neurology collaboration.</div>

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    </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;">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 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 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;">For each program under this collaboration, we are eligible to receive a license fee, development milestone payments and regulatory
    milestone payments, plus a mark-up on the costs 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, 2023, we have generated more than $230 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-style: italic; 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;">WAINUA (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 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for
    the treatment of ATTR. In December 2023, the FDA approved eplontersen with the brand name, WAINUA, in the U.S. for ATTRv-PN. We are jointly developing and commercializing WAINUA with AstraZeneca in the U.S. We initially granted AstraZeneca exclusive
    rights to commercialize WAINUA outside the U.S., except for certain Latin American countries. In July 2023, we expanded those rights to include Latin America.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The collaboration 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
    WAINUA 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;">Over the term of the collaboration, we are eligible to receive an upfront payment, license fee, development and approval milestone
    payments and 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 ranging from mid to high teens for sales outside the U.S. From inception through December 31, 2023, we have generated more than $425 million in payments under this collaboration, including a milestone payment for the approval of WAINUA
    in the U.S. and revenue we earned from cost sharing provisions.</div>

  <div><br/>
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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;">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 WAINUA, we have a collaboration with AstraZeneca focused on discovering and developing treatments for
    cardiovascular, renal and metabolic diseases, which we formed in 2015. 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&#160; an upfront payment, license fees, development milestone payments and
    regulatory 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, 2023, we have generated more than $340 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 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. Under our collaboration, GSK is developing bepirovirsen for the treatment of chronic 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 an upfront payment, a license fee, development milestone payments,
    regulatory milestone payments and sales milestone payments if GSK successfully develops and commercializes 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, 2023, we have generated more than $105 million in payments under the HBV program collaboration.</div>

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    </div>

  </div>

  <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; font-style: italic;">Pelacarsen Collaboration</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2017, we initiated a collaboration with Novartis to develop and commercialize pelacarsen. 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 2019.</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 an upfront payment, a&#160; license fee, a development milestone payment, regulatory milestone payments and 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</span>. From inception through December 31, 2023, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e
      have generated more than $275 million in payments under this collaboration.</span></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; font-style: italic;">New Medicine for the Treatment of Lp(a)-Driven Cardiovascular Disease</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2023, we entered into a collaboration and license agreement with Novartis for the discovery, development and commercialization
    of a novel medicine for patients with Lp(a)-driven cardiovascular disease, or CVD. Novartis is solely responsible for the development, manufacturing and potential commercialization of the next generation Lp(a) therapy.</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 an upfront payment, development milestone payments, regulatory milestone
    payments and sales milestone payments. In addition, we are eligible to receive tiered royalties ranging from 10 percent to 20 percent on net sales. From inception through December 31, 2023, we have generated $60 million in payments under this collaboration.</div>

  <div><br/>
  </div>

  <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 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 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. As a result, Roche is responsible for all 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 a license fee, development milestone payments, regulatory milestone
      payments and sales milestone payments as tominersen advances. In addition, we are eligible to receive 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 collaboration. From inception through December 31, 2023, we have generated more than $150 million&#160;
      in payments under this collaboration.</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;">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 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 IgAN and one for the treatment of patients with GA, the advanced stage of dry AMD. In April 2023, Roche
    initiated a Phase 3 study of IONIS-FB-L<sub>Rx</sub> in patients with IgAN.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After positive data from a Phase 2 clinical study in patients with IgAN, Roche licensed IONIS-FB-L<sub>Rx</sub> in 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 an upfront payment, a&#160; license fee, development milestone payments,
    regulatory milestone payments and 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, 2023, we have generated more than $135 million&#160; 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;">RNA-Targeting Medicines for Alzheimer's Disease and Huntington's Disease</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2023, we entered into an agreement with Roche to develop two undisclosed early-stage programs for RNA-targeting
    investigational medicines for the treatment of AD and HD. Under the agreement, we are responsible for advancing the two programs through preclinical studies and Roche is responsible for clinical development, manufacturing and commercialization of the
    medicines if they receive regulatory 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 an upfront payment, development milestone payments and sales milestone
    payments. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales. From inception through December 31, 2023,
    we have generated $60 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-style: italic; font-weight: bold;">Commercialization Partnerships</div>

  <div><br/>
  </div>

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

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2023, we entered into an agreement with Otsuka Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe.
    We are responsible for the ongoing development of donidalorsen. We retained the rights to commercialize donidalorsen in the U.S. and in the rest of the world assuming regulatory 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 an upfront payment, regulatory milestone payments and sales milestone
    payments. In addition, we are eligible to receive tiered royalties ranging from 20 percent to 30 percent on net sales of donidalorsen in Europe. From inception through December 31, 2023, we have generated $65 million in payments under this collaboration.</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;">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-20 percent range on net sales for each medicine. In December 2021 and September 2023, we started receiving royalties from PTC
    for TEGSEDI and WAYLIVRA sales, respectively.</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. Refer to the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Overview</span>, for further details on our distribution agreement with Sobi.</div>

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    </div>

  </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;">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</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 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 2021, we exercised our option to license Bicycle's technology. Our payment to Bicycle for licensing its technology included an equity investment in Bicycle.</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 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 Metagenomi to license its technologies and will pay
    Metagenomi certain fees for the selection of genetic targets. In addition, we will pay Metagenomi milestone payments and royalties that are contingent on the achievement of certain development, regulatory and sales events. We will also 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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Vect-Horus</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2023, we entered into a license agreement with Vect-Horus to provide us with worldwide, exclusive license for a specified
    number of targets using Vect-Horus&#8217; platform technology &#8221;VECTrans&#8221; for systemic delivery of RNA-targeted therapeutics that can cross the blood-brain barrier and address targets in the central nervous system. As a result, we paid Vect-Horus to license
    its technologies. In addition, we will pay Vect-Horus milestone payments and royalties that are contingent on the achievement of certain development, regulatory and sales events.</div>

  <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;">Other Agreements</div>

  </div>

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

  </div>

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

  </div>

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

  <div style="text-align: justify;"><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, or R&amp;D, 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.</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><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 and/or our CMOs 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 CMOs 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 CMOs.</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 CMOs 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 commercial medicines 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">QALSODY</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 QALSODY 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;">WAINUA</div>

  <div><br/>
  </div>

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

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    </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;">Olezarsen, Donidalorsen, Zilganersen, Ulefnersen</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 our CMOs have supplied the API and the finished
      drug product for </span>olezarsen, donidalorsen, zilganersen and ulefnersen 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 maintain long-term supply at competitive prices in the future.</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;">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 API and 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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bepirovirsen</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We supplied API for bepirovirsen&#8217;s Phase 1 and Phase 2 programs. Pursuant to our collaboration with GSK, GSK is responsible for any
    further bepirovirsen 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;">IONIS-FB-L<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;">We supplied API for the IONIS-FB-L<sub>Rx</sub> Phase 1 and Phase 2 IgAN programs. Pursuant to our collaboration with Roche, Roche is
    responsible for any further drug supply for the IONIS-FB-L<sub>Rx</sub> program.</div>

  <div><br/>
  </div>

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

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have established sales and marketing capabilities to support our commercial launch of WAINUA in the U.S. and anticipated near-term
    commercial launches of olezarsen and donidalorsen. We began with our co-commercialization partnership with AstraZeneca for WAINUA in which we combine our experience in RNA-targeted therapeutics and deep knowledge of the TTR amyloidosis market with
    AstraZeneca's global scale in drug development and commercialization to enable market penetration for the benefit of patients.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As we approach our first potential independent commercial launches of olezarsen and donidalorsen in the U.S., we have been refining our
    portfolio strategy and recruiting experienced professionals with relevant backgrounds in sales, marketing, patient education, market access, portfolio planning and market insight, new product commercial strategy and commercial operations in the
    pharmaceutical industry. We are focused on developing a unique and innovative approach to bring our medicines to patients living with serious diseases. We have built core capabilities and a commercial platform with the ability to scale as needed to
    meet our current and future commercialization needs. We plan to build our field sales teams as we approach each of our launches.</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 recently entered into a European licensing agreement with Otsuka for donidalorsen in HAE in which we will leverage
    Otsuka's strong commercial infrastructure and rare disease experience to reach European HAE patients.</div>

  <div><br/>
  </div>

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

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have built medical affairs capabilities to disseminate information about our medicines and increase disease awareness through various
    channels of communication with key stakeholders. Our medical affairs function is responsible for funding and coordinating investigator-sponsored trials, communicating scientific and clinical information to healthcare providers, medical professionals
    and patients, and managing publications.</div>

  <div><br/>
  </div>

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

  <div style="text-align: justify;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We rely on patents, trademarks, trade secrets, and proprietary know-how to develop and maintain a competitive position in RNA-targeted
    therapeutics generally and to protect our investment in specific products. To this end, we focus our resources on intellectual property, or IP, that drives value for our company.</div>

  <div><br/>
  </div>

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

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Each of our medicines is protected worldwide by product-specific patents claiming oligonucleotides having the nucleobase sequences and
    chemical modifications of our medicines; and methods of achieving cellular or clinical endpoints using such oligonucleotides. We pursue such patents 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 regulatory review. Expiration dates listed below do not reflect any such extensions.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial products are also protected by trademarks filed throughout the world.</div>

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    </div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Marketed Products</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 2</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;">Patents</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 (nusinersen) 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, (ii) joint patents with Cold Spring Harbor Laboratory claiming fully modified 2&#8217;-MOE compounds targeting SMN2, including the precise composition of matter of SPINRAZA and methods of using such compositions; and (iii) dosing and therapeutic methods
    of using such compounds and compositions. 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>

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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>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

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    <td style="width: 31%; 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>
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          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 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: #FFFFFF;">&#160;</td>

    <td style="width: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 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: #CCEEFF;">&#160;</td>

    <td style="width: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 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: #FFFFFF;">&#160;</td>

    <td style="width: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 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: #FFFFFF;">&#160;</td>

    <td style="width: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 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: #CCEEFF;">&#160;</td>

    <td style="width: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 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: #FFFFFF;">&#160;</td>

    <td style="width: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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;">Trademarks</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The name &#8220;SPINRAZA&#8221; is protected throughout the world by trademarks owned by our commercial partner Biogen. Particulars for the United
    States and European marks are listed below:</div>

  <div><br/>
  </div>

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


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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: 2%; vertical-align: bottom;">&#160;</td>

    <td style="width: 22%; 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;">Registration No.</div>
        </td>

    <td style="width: 2%; vertical-align: bottom;">&#160;</td>

    <td style="vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" colspan="3">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Mark</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; 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: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5156572</div>
        </td>

    <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA</div>
        </td>

    <td style="width: 2.36%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman'; font-size: 2pt;">_</div>
        </td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(word mark)</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; 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: 2%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">013388145</div>
        </td>

    <td style="width: 2%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA</div>
        </td>

    <td style="width: 2.36%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(word mark)</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 2%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">014812291 and 015309941</div>
        </td>

    <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: right;"><img width="114" height="30" src="image11.jpg" alt="graphic"/></div>
        </td>

    <td style="width: 2.36%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(design mark)</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;">QALSODY 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; font-style: italic;">Patents</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe QALSODY is protected from generic competition in the U.S. and Europe until at least 2035. Additional patent applications
    designed to protect QALSODY in other foreign jurisdictions are being pursued. With Biogen&#8217;s license of QALSODY, 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 QALSODY</span> 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%; border-collapse: collapse; text-align: left; color: #000000;">


  <tr>

    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; 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>
          <div>&#160;</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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 QALSODY</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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 QALSODY</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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 QALSODY</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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;">Composition of </span>QALSODY</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;">Trademarks</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The name &#8220;QALSODY&#8221; is protected throughout the world by trademarks owned by our commercial partner Biogen.&#160; Particulars for the United
    States and European marks are listed below:</div>

  <div><br/>
  </div>

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


  <tr>

    <td style="width: 22%; 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;">Jurisdiction</div>
        </td>

    <td style="width: 2%; vertical-align: bottom;">&#160;</td>

    <td style="width: 22%; 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;">Registration No.</div>
        </td>

    <td style="width: 2%; vertical-align: bottom;">&#160;</td>

    <td style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="3">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Mark</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; 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: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7164425</div>
        </td>

    <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">QALSODY</div>
        </td>

    <td style="width: 2.36%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman'; font-size: 2pt;">_</div>
        </td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(word mark)</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 2%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7116182</div>
        </td>

    <td style="width: 2%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: right;"><img width="64" height="34" src="image14.jpg" alt="graphic"/></div>
        </td>

    <td style="width: 2.36%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(design mark)</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1542485</div>
        </td>

    <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">QALSODY</div>
        </td>

    <td style="width: 2.36%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(word mark)</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; vertical-align: middle; 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: 2%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">018517819</div>
        </td>

    <td style="width: 2%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: right;"><img width="64" height="34" src="image14.jpg" alt="graphic"/></div>
        </td>

    <td style="width: 2.36%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(design mark)</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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; font-weight: bold;">WAINUA <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">and
      Transthyretin</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;">Patents</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe WAINUA (eplontersen) is protected from generic competition in the U.S. and Europe until at least 2034. Additional patent
    applications to protect WAINUA in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting WAINUA 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%; border-collapse: collapse; text-align: left; color: #000000;">


  <tr>

    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Trademarks</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The name &#8220;WAINUA&#8221; is protected by trademarks owned by our commercial partner Astra Zeneca. Particulars for the United States marks are
    listed below:</div>

  <div><br/>
  </div>

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


  <tr>

    <td style="width: 22%; 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;">Jurisdiction</div>
        </td>

    <td style="width: 2%; vertical-align: bottom;">&#160;</td>

    <td style="width: 22%; 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;">Application No.</div>
        </td>

    <td style="width: 2%; vertical-align: bottom;">&#160;</td>

    <td style="vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" colspan="3">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Mark</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; 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: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">98054331</div>
        </td>

    <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA</div>
        </td>

    <td style="width: 2.36%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman'; font-size: 2pt;">_</div>
        </td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(word mark)</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 2%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">98228658</div>
        </td>

    <td style="width: 2%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: right;"><img width="42" height="34" src="image13.jpg" alt="graphic"/></div>
        </td>

    <td style="width: 2.36%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(design mark)</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;">TEGSEDI and Transthyretin</div>

  <div style="text-align: justify;"><br/>
  </div>

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

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe TEGSEDI (inotersen) is protected from generic competition in the U.S. and Europe until at least 2031. 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%; border-collapse: collapse; text-align: left; color: #000000;">


  <tr>

    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <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: 31%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <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: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <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: 31%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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 TEGSEDI</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 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: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,697,860</div>
        </td>

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

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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 TEGSEDI</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,061,044</div>
        </td>

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

    <td style="width: 31%; 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 TRANSTHYRETIN EXPRESSION</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 10%; vertical-align: top; background-color: rgb(255, 255, 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: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,399,774</div>
        </td>

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

    <td style="width: 31%; 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 TRANSTHYRETIN EXPRESSION</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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 transthyretin amyloidosis by administering TEGSEDI</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 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: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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 TRANSTHYRETIN EXPRESSION</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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 TEGSEDI</div>
        </td>

  </tr>


</table>
  <div style="text-align: left; text-indent: 36pt;"><br/>
  </div>

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

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The name &#8220;TEGSEDI&#8221; is protected by trademark throughout the world. Particulars for the United States and European marks are listed below:</div>

  <div><br/>
  </div>

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


  <tr>

    <td style="width: 22%; 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;">Jurisdiction</div>
        </td>

    <td style="width: 2%; vertical-align: bottom;">&#160;</td>

    <td style="width: 22%; 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;">Registration No.</div>
        </td>

    <td style="width: 2%; vertical-align: bottom;">&#160;</td>

    <td style="vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" colspan="3">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Mark</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; 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: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5740635</div>
        </td>

    <td style="width: 2%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI</div>
        </td>

    <td style="width: 2.36%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman'; font-size: 2pt;">_</div>
        </td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(word mark)</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; 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: 2%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">017224742</div>
        </td>

    <td style="width: 2%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI</div>
        </td>

    <td style="width: 2.36%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(word mark)</div>
        </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;">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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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; font-weight: bold;">WAYLIVRA and Apolipoprotein C-III</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;">Patents</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe WAYLIVRA (volanesorsen) is protected from generic competition in Europe until at least 2034. 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. 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%; border-collapse: collapse; text-align: left; color: #000000;">


  <tr>

    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 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: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: #CCEEFF;">&#160;</td>

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: #FFFFFF;">&#160;</td>

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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 that hybridize within the nucleotide region of apo-CIII targeted by WAYLIVRA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 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: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: #CCEEFF;">&#160;</td>

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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 complementary to an apo-CIII nucleic acid for use in therapy</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 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: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,157,082</div>
        </td>

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

    <td style="width: 31%; 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</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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 apo-CIII antisense compounds for reducing pancreatitis and chylomicronemia and increasing HDL</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,593,333</div>
        </td>

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

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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 lipoprotein lipase deficiency with an apo-CIII specific inhibitor wherein triglyceride levels are reduced</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: #FFFFFF;">&#160;</td>

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Apo-CIII specific inhibitors including WAYLIVRA for treating lipoprotein lipase deficiency or FCS</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;">Trademark</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The name &#8220;WAYLIVRA&#8221; is protected by trademark in Europe. Particulars for the European mark are listed below:</div>

  <div><br/>
  </div>

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


  <tr>

    <td style="width: 22%; 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;">Jurisdiction</div>
        </td>

    <td style="width: 2%; vertical-align: bottom;">&#160;</td>

    <td style="width: 22%; 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;">Registration No.</div>
        </td>

    <td style="width: 2%; vertical-align: bottom;">&#160;</td>

    <td style="vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" colspan="3">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Mark</div>
        </td>

  </tr>

  <tr>

    <td style="width: 22%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 2%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">016409609</div>
        </td>

    <td style="width: 2%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAYLIVRA</div>
        </td>

    <td style="width: 2.36%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 25%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(word mark)</div>
        </td>

  </tr>


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

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Phase 3 Programs</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;">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%; border-collapse: collapse; text-align: left; color: #000000;">


  <tr>

    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,163,239</div>
        </td>

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

    <td style="width: 31%; 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 C-III EXPRESSION</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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 olezarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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 C-III EXPRESSION</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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 olezarsen</div>
        </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;">33</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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; 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%; border-collapse: collapse; text-align: left; color: #000000;">


  <tr>

    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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;">Zilganersen and GFAP</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe zilganersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> is protected from generic competition
      in the U.S. until at least 2041. </span>A patent application designed to protect zilganersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>from generic competition is being pursued in Europe; a patent issuing
    from that application would have term until at least 2041. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The table below lists a key issued patent protecting </span>zilganersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in the U.S. and a pending application in Europe:</span></div>

  <div><br/>
  </div>

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


  <tr>

    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Patent Application No.)</div>
        </td>

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

    <td style="width: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; 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: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,786,546</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; 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 MODULATING GFAP</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2041</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;Composition of zilganersen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(20846055.0)</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; 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 MODULATING GFAP</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2041</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; 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 zilganersen</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;">Ulefnersen and FUS</div>

  <div style="text-align: justify; text-indent: 36pt;"><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 ulefnersen 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 ulefnersen</span> in the U.S. and
    Europe:</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

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


  <tr>

    <td style="width: 10%; 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: 10%; 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 Application No.</div>
        </td>

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

    <td style="width: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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 ulefnersen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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 ulefnersen</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;">34</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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; 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%; border-collapse: collapse; text-align: left; color: #000000;">


  <tr>

    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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: 10%; 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>
          <div>&#160;</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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: 10%; 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>
          <div>&#160;</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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; font-style: italic; font-weight: bold;">Bepirovirsen and Hepatitis B Virus</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe bepirovirsen<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 2032. Additional patent protection designed to protect bepirovirsen in other foreign jurisdictions are being pursued. With GSK&#8217;s license of bepirovirsen, we assigned our interest in these patents to GSK. The
      table below lists some key issued patents protecting </span>bepirovirsen<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%; border-collapse: collapse; text-align: left; color: #000000;">


  <tr>

    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; margin-right: 3.25pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,642,752</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; 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 HEPATITIS B VIRUS (HBV) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; 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 bepirovirsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3505528</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; 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 HEPATITIS B VIRUS (HBV) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; 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 bepirovirsen</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;">IONIS-FB-L<sub>Rx</sub> and Factor B</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe IONIS-FB-L<sub>Rx</sub><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 2035. Additional patent protection designed to protect </span>IONIS-FB-L<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in other foreign jurisdictions are
      being pursued. The table below lists some key issued patents protecting </span>IONIS-FB-L<sub>Rx</sub><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%; border-collapse: collapse; text-align: left; color: #000000;">


  <tr>

    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3043827</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATORS OF COMPLEMENT FACTOR B</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; 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;">Compound comprising the antisense oligonucleotide portion of </span>IONIS-FB-L<sub>Rx</sub>.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 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: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,280,423</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; 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 COMPLEMENT FACTOR B EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 31%; 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;">Composition of </span>IONIS-FB-L<sub>Rx</sub>.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 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: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3137596</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; 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 COMPLEMENT FACTOR B EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 31%; 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 </span>IONIS-FB-L<sub>Rx</sub>.</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;">35</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Platform IP</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 the IP that provides exclusivity for specific products, we also pursue IP that provides 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 designs utilizing these chemical modifications. Because these core claims are
    independent of specific therapeutic target, nucleic acid sequence, or clinical indication, they may reach several products.</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;">Chemically Modified Nucleosides and Oligonucleotides</div>

  <div style="text-align: justify; text-indent: 36pt;"><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. The following are some of our patents in this category 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%; border-collapse: collapse; text-align: left; color: #000000;">


  <tr>

    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,399,845</div>
        </td>

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

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
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    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
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    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
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        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
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    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
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    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
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    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
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        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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>

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    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,022,193</div>
        </td>

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    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
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    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
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    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
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        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
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        </td>

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    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
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    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
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    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
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        </td>

  </tr>

  <tr>

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

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    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2314594</div>
        </td>

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    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
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    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
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    <td style="width: 31%; 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 containing cEt nucleoside analogs and methods of use</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 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: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: #FFFFFF;">&#160;</td>

    <td style="width: 31%; 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 SYNTHESIS OF BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
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    <td style="width: 31%; 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 synthesizing cEt nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 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: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 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: #CCEEFF;">&#160;</td>

    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
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    <td style="width: 31%; 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 2&#8217;-modifed and LNA nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 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: #FFFFFF;">&#160;</td>

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
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        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

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    <td style="width: 31%; 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 wings comprised of 2&#8217;-MOE and bicyclic nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 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: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2410054</div>
        </td>

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    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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 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: 10%; vertical-align: top; background-color: rgb(255, 255, 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: #FFFFFF;">&#160;</td>

    <td style="width: 10%; 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: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2028</div>
        </td>

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    <td style="width: 31%; 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: 10%; 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: 10%; 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: 31%; 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>

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    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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: 10%; 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: 10%; 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>

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    <td style="width: 31%; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; 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>

  <tr>

    <td style="width: 10%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,629,348</div>
        </td>

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    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">LINKAGE MODIFIED OLIGONUCLEOTIDES AND USES THEREOF</div>
        </td>

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    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; 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 2-4 mesyl phosphoramidate internucleoside linkages at specified positions in the gap</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;">36</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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; font-weight: bold;">LIgand-Conjugated Antisense (LICA) Technology</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" border="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">


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    <td style="width: 10%; 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;">Jurisdiction</div>
        </td>

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

    <td style="width: 10%; 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: 31%; 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>

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    <td style="width: 10%; 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;">Expiration</div>
        </td>

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

    <td style="width: 31%; 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: 10%; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,127,276</div>
        </td>

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

    <td style="width: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 10%; vertical-align: top; background-color: rgb(255, 255, 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: #FFFFFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,181,549</div>
        </td>

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

    <td style="width: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 31%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 10%; vertical-align: top; background-color: rgb(204, 238, 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: #CCEEFF;">&#160;</td>

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 31%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Manufacturing</div>

  <div style="text-align: justify; text-indent: 36pt;"><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 and related compounds. These patents claim methods
    for improving oligonucleotide drug manufacturing, including processes for large-scale oligonucleotide synthesis and purification.</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;"><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;"><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;"><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;"><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. 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>

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    </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;">Pricing and Reimbursement</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 that 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. Moreover, a payer's decision to provide coverage for a medicine does not imply that an adequate reimbursement rate
    will be approved. Additionally, coverage and reimbursement for drugs can differ significantly from payer to payer. One third-party payer's decision to cover a particular medicine does not ensure that other payers will also provide coverage for the
    medicine or will provide coverage at an adequate reimbursement rate.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Third-party payers are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medicines and
    services, in addition to their safety and efficacy. To obtain coverage and reimbursement for any medicine that might be approved for sale, we may need to conduct expensive pharmacoeconomic studies to demonstrate the medical necessity and
    cost-effectiveness of our medicine. These studies will be in addition to the studies required to obtain regulatory approvals. If third-party payers do not consider a medicine to be cost-effective compared to other available therapies, they may not
    cover the medicine after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to sell such medicine at a profit.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In certain jurisdictions, governments may also regulate or influence coverage, reimbursement and/or pricing of our medicines to control
    cost or affect use. In the European community, governments influence the price of drugs through their pricing and reimbursement rules and control of national health care systems that fund a large part of the cost of those medicines to consumers. Some
    jurisdictions operate positive and negative list systems under which medicines may only be marketed once a reimbursement price has been agreed to by the government. To obtain reimbursement or pricing approval, some of these countries may require the
    completion of clinical studies that compare the cost effectiveness of a particular drug candidate to currently available therapies. Other member states allow companies to fix their own prices for medicines but monitor and control company profits.</div>

  <div style="text-align: justify; text-indent: 36pt; margin-top: 12pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The marketability of any medicine for which we receive regulatory approval for commercial sale may suffer if the
    government and third-party payers fail to provide adequate coverage and reimbursement. In addition, the focus on cost containment measures in the U.S. and other countries has increased and we expect will continue to increase the pressure on
    pharmaceutical pricing. Coverage policies and third-party reimbursement rates may change at any time. Even if we attain favorable coverage and reimbursement status for one or more medicines for which we receive regulatory approval, less favorable
    coverage policies and reimbursement rates may be implemented in the future.</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;">Healthcare Reform</div>

  <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 report that outlined principles for drug pricing reform and set out a variety of potential legislative policies that Congress could
    pursue as well as potential administrative actions HHS could take to advance 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>

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    </div>

  </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. 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; Specifically, in an effort to curb Medicare patients&#8217; out-of-pocket costs for prescription drugs, the Part D redesign legislation under the IRA requires, among other
    things, (1) a cap on out-of-pocket drug spending under Part D, (2) drug manufacturers to pay a rebate to the federal government if prices for drugs covered under Part D and Part B increase faster than the rate of inflation, and (3) drug manufacturers
    to contribute to the catastrophic coverage phase for Part D drugs as discounts through a manufacturer discount program. The IRA permits HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years. These
    provisions take effect progressively starting in fiscal year 2023. On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject
    to legal challenges. In response to the Biden administration&#8217;s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center which will be evaluated on their ability to
    lower the cost of drugs, promote accessibility, and improve quality of care. It is unclear whether the models will be utilized in any health reform measures in the future. Further, on December 7, 2023, the Biden administration announced an initiative
    to control the price of prescription drugs using march-in rights under the Bayh-Dole Act. On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise
    of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights. While march-in rights have not previously been exercised, it is uncertain if that will continue under
    the new framework.</div>

  <div><br/>
  </div>

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

  <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 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>

  </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;">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>

  </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;">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>

  </tr>


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    </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;">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 tested and the FDA approved. 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>

  <div><br/>
  </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, 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. Further, HIPAA also 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. 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, corporate integrity agreements, and could
    include criminal penalties. 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. As described above, other healthcare laws that may affect our ability to operate include
    HIPAA, 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. 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: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed above, 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, including new models aimed to lower of cost of drugs, promote accessibility, and improve quality of care and initiatives to control the price of prescription drugs using
    march-in rights under the Bayh-Dole Act.</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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;">The Foreign Corrupt Practices Act</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. In addition, 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 contract research organizations, contract manufacturing organizations, distributors, wholesalers, agents, contractors and other partners) will comply with anti-bribery
    laws. Importantly, we do not control the actions of manufacturers and other third-party agents, although we may be liable for their actions.</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>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our commercial medicines and our medicines in 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.</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/>
  </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: 10%; 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: 26%; 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: 19%; 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: 19%; 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>

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    <td style="width: 17.78%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Zolgensma</div>
          <div style="text-align: left; 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: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <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: 26%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <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: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <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: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Evrysdi</div>
          <div style="text-align: left; 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: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 26%; vertical-align: top; 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 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: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <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: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">OAV101</div>
          <div style="text-align: left; 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: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 19%; vertical-align: top; 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: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intrathecal injection</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>

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  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">QALSODY</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 QALSODY in SOD1-ALS:</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: 10%; 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: 26%; 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: 19%; 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: 19%; 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>

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    <td style="width: 17.78%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NI-005 / AP-101</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Neurimmune (AL-S Pharma) / Lilly</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <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><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">WAINUA and TEGSEDI</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 WAINUA and TEGSEDI for ATTRv-PN and/or ATTR-CM:</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: 10%; 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: 26%; 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: 19%; 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: 19%; 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: 17.78%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Onpattro</div>
          <div style="text-align: left; 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: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 26%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Received CRL in the U.S. for ATTR-CM</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved in US, EU, Japan and select other markets for ATTRv-PN</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vyndaqel/Vyndamax</div>
          <div style="text-align: left; 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: 10%; vertical-align: top; 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: 26%; vertical-align: top; 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: 19%; vertical-align: top; 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, ATTR-CM; indications vary by region</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amvuttra</div>
          <div style="text-align: left; 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: 10%; vertical-align: top; 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: 26%; vertical-align: top; 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: 19%; vertical-align: top; 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., EU and Japan, Phase 3 for ATTR-CM</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; 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: 10%; vertical-align: top; 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: 26%; vertical-align: top; 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: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Submitted in U.S., EU and Japan</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NTLA-2001</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CRISPR therapeutic candidate designed to reduce circulating TTR protein levels</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 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: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ALXN2220</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A monoclonal IgG1 which acts by targeting and depleting TTR protein</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NNC6019-0001</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A monoclonal antibody to deplete amyloid via antibody-mediated phagocytosis</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 ATTR-CM</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 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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    <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;">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/>
  </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: 10%; 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: 26%; 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: 19%; 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: 19%; 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: 17.78%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ARO-APOC3</div>
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Plozasiran)</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Arrowhead</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pegozafermin</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 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(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 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(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 SHTG</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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>


</table>
  <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: 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>


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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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;">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/>
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    <td style="width: 17.78%; 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: 10%; 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: 26%; 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: 19%; 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: 19%; 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: 17.78%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Takhzyro</div>
          <div style="text-align: left; 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: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 26%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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 two years and older</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cinryze</div>
          <div style="text-align: left; 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: 10%; vertical-align: top; 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: 26%; vertical-align: top; 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: 19%; vertical-align: top; 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: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Orladeyo</div>
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(berotralstat)</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; 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: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; 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: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Haegarda</div>
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(C1 esterase inhibitor)</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; 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: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; 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: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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 6 years and older</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Garadacimab</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; 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: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; 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: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under regulatory review in the U.S. and EU</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

  </tr>

  <tr>

    <td style="width: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deucrictibant</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An oral B2-receptor antagonist</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">STAR-0215</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A monoclonal antibody inhibitor of plasma kallikrein</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NTLA-2002</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 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: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 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: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 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: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>


</table>
  <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: 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;">Zilganersen</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 are no medicines in clinical development for AxD.</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;">Ulefnersen</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 are no medicines in clinical development for FUS-ALS.</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;">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>

  <div><br/>
  </div>

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


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    <td style="width: 17.78%; 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: 10%; 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: 26%; 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: 19%; 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: 19%; 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: 17.78%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; 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: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amgen/ Arrowhead</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Zerlasiran</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; 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: 19%; vertical-align: top; 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: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lepodisiran</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; 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: 19%; vertical-align: top; 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: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Muvalaplin</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Small molecule therapy 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: 19%; vertical-align: top; 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: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>


</table>
  <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: 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 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;">43</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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;">Bepirovirsen</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 bepirovirsen in HBV:</div>

  <div><br/>
  </div>

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    <td style="width: 17.78%; 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: 10%; 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: 26%; 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: 19%; 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: 19%; 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: 17.78%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elebsiran</div>
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(VIR-2218)</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vir Biotech / Alnylam</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RNAi therapeutic to reduce HBV viral antigens</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Imdusiran</div>
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(AB-729)</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RNAi therapeutic to reduce HBV viral antigens</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Xalnesiran</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RNAi therapeutic to reduce HBV viral antigens</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; 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>

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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: left;">
          <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;">IONIS-FB-L<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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We believe that the following medicines could compete with I</span>ONIS-FB-L<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in IgAN:</span></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: 10%; 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: 26%; 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: 19%; 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: 19%; 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: 17.78%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tarpeyo (budesonide)</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Calliditas</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A corticosteroid indicated to reduce proteinuria in adults with primary IgAN</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for IgAN</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Filspari<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><br/>
            </span>(Sparsentan)</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An endothelin &amp; angiotensin II receptor antagonist to reduce proteinuria in adults with primary IgAN</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for IgAN</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Atrasentan</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An endothelin A receptor antagonist</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Iptacopan</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A factor B inhibitor of the alternative complement pathway</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Zigakibart</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An anti-APRIL monoclonal antibody</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sibeprenlimab</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A humanized IgG2 monoclonal antibody that inhibits APRIL</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Atacicept</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A recombinant fusion protein a dual inhibitor of BLyS and APRIL</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (IgAN)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ravulizumab</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A humanized monoclonal antibody to complement factor 5</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 (IgAN)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vemircopan</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A complement factor D inhibitor</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 (IgAN)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Felzartamab</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A monoclonal antibody directed against CD38</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 (IgAN)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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>

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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: left;">
          <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: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">44</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

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  <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;">We believe that the following medicines could compete with I</span>ONIS-FB-L<sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in GA:</span></div>

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    <td style="width: 17.78%; 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;">Medicine</div>
        </td>

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

    <td style="width: 10%; 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: 26%; 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: 19%; 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: 19%; 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>

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    <td style="width: 17.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ivervay (avacincaptad pegol)</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A complement C5 inhibitor approved for GA secondary to AMD</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved (GA)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravitreal</div>
        </td>

  </tr>

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    <td style="width: 17.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Syfovre (pegcetacoplan)</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A complement C5 inhibitor approved for GA secondary to AMD</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved (GA)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravitreal</div>
        </td>

  </tr>

  <tr>

    <td style="width: 17.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tinlarebant</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A small molecule RBP4 antagonist</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 (GA)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; 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: 17.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Danicopan</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A factor D inhibitor</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 (GA)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 17.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">PPY988 (GT005)</div>
        </td>

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

    <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <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: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A gene therapy with encoding for human complement factor I</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 (GA)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intraocular</div>
        </td>

  </tr>

  <tr>

    <td style="width: 17.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AVD-104</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A glycomimetic nanoparticle</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 (GA)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravitreal</div>
        </td>

  </tr>

  <tr>

    <td style="width: 17.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANX007</div>
        </td>

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

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

    <td style="width: 2.42%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A fragment antigen-binding (fab) antibody</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 (GA)</div>
        </td>

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

    <td style="width: 19%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravitreal</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: left;">
          <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><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Corporate Responsibility and 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 believe operating responsibly and sustainably creates long-term value for our company and our stakeholders. We recognize the importance
    of Corporate Responsibility, or CR, and Environmental, Social and Governance, or ESG, initiatives as it relates to our business strategy and risk assessment. In 2023, we continued to evolve our CR program by building on our foundation and further
    defining our strategic direction. This includes completing our first CR materiality assessment, updating our CR framework to better focus on our ESG priorities and developing goals to drive and measure our performance.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We began reporting on CR metrics in 2021 and have continued to expand disclosure since then. In 2023, we established three strategic CR
    pillars that we believe are most important to our business:</div>

  <div><br/>
  </div>

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

  <div><br/>
  </div>

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    <td style="width: 33.33%; 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; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Innovate to improve the lives </div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of people with serious diseases</div>
        </td>

    <td style="width: 34%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Empowering our</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">employees and communities</div>
        </td>

    <td style="width: 33.33%; 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; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Operating</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">responsibly and sustainably</div>
        </td>

  </tr>

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    <td style="width: 33.33%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We innovate across the business and work tirelessly to discover, develop and deliver important new medicines for
            people with serious diseases.</div>
        </td>

    <td style="width: 34%; 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: left; margin-left: 4.2pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We are committed to fostering an inclusive culture that drives excellence, embraces diversity, and supports our
            communities.</div>
        </td>

    <td style="width: 33.33%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">We operate with integrity to help create a better, more sustainable future for all through environmental
            stewardship and responsible business practices and stakeholder interactions.</div>
        </td>

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    <td style="width: 33.33%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #FFFFFF;">
          <div style="text-indent: 4.5pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Innovation and R&amp;D</span></div>
          <div style="text-indent: 4.5pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Access and Affordability</span></div>
          <div style="text-indent: 4.5pt;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 12pt;">&#8226;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Patient Advocacy and Engagement</span></div>
        </td>

    <td style="width: 34%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(255, 255, 255);">
          <div style="text-indent: 4.2pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Workplace Culture, Talent Attraction and Development</span></div>
          <div style="text-indent: 4.2pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Diversity, Equity and Inclusion</span></div>
          <div style="text-indent: 4.2pt;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 12pt;">&#8226;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Social Impact and Community Engagement</span></div>
        </td>

    <td style="width: 33.33%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #FFFFFF;">
          <div style="text-indent: 4.5pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Environmental Sustainability</span></div>
          <div style="text-indent: 4.5pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8226;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Governance and Integrity</span></div>
          <div style="text-indent: 4.5pt;"><span style="font-family: 'Times New Roman', Times, serif; font-size: 12pt;">&#8226;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 9pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Data Privacy and Cybersecurity</span></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;">Our CR initiatives are driven by our Chief Executive Officer and executive-level CR Steering Committee, or CR Committee. The CR Committee
    consists of senior leaders in key functions across the company, including legal, finance, investor relations, human resources, research and development, manufacturing, commercial, compliance and corporate affairs. In 2023, we expanded our CR Committee
    to include a broader cross-section of senior leaders to ensure we continue to develop the right programs and policies.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The CR Committee is 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. Our Board of Directors oversees our overall CR strategy and management of material ESG risks and opportunities and receives updates related to corporate governance and corporate
    responsibility from the CR Committee at least once annually. In 2023, the Nominating, Governance and Review Committee assumed responsibility for CR and ESG-related matters.</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </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 will share more details on our updated CR framework, goals and ESG initiatives in our 2023 CR Report, which will be published in April
    2024 and available on our website. Nothing in the report or 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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Employees and Human Capital</div>

  <div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of February 15, 2024, we
    employed 927 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 2023 was 7 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: 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: 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>
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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: 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>


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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: 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>
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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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Wellness programs;</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: 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>
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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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Family care benefits;</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: 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>
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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: 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, ethnicity, race, age 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;">On an annual basis, we monitor our pay equity status and market competitiveness, and perform a pay equity analysis that reviews pay equity
    by gender, ethnicity, race and age. Our 2023 pay equity analysis confirmed we do not have a statistically significant difference in pay for the same or similar work, regardless of gender, ethnicity, race or age.</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>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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; 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>

  <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;"><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 15, 2024:</div>

  <div style="text-align: left;"><br/>
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          <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;">62</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;">46</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;">Brian Birchler</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;">58</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, Corporate and Development Operations</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;">C. Frank Bennett, Ph.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;">67</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 Scientific 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;">Onaiza Cadoret-Manier</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;">59</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 Global Product Strategy and Operations 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;">Richard S. Geary, Ph.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;">66</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 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;">Elizabeth L. Hougen</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;">62</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, Finance and Chief Financial 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;">Patrick R. O&#8217;Neil, Esq.</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;">Chief Legal Officer, General Counsel and Corporate Secretary</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;">Eugene Schneider, M.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;">51</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, Chief Clinical Development and Operations 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;">Eric E. Swayze, Ph.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;">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: 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;"><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, M.A., M.B.A., M.S.</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;"><br/>
  </div>

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

  <div style="text-align: justify;"><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, Corporate and Development Operations</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mr. Birchler has served as Ionis&#8217; Executive Vice President, Corporate and Development Operations since March 2022. From January 2008 to
    March 2022, Mr. Birchler served as our Senior Vice President, Drug Development Operations. From January 2005 to January 2008 he served as our Vice President, Drug Development Operations and from January 2003 to January 2005, as our Vice President,
    Development Chemistry and Operations. Mr. Birchler joined Ionis in 1995 as Senior Scientist/Senior Research Associate. Prior to joining Ionis, Mr. Birchler was employed by CIBA Vision Corp. and Burroughs Wellcome Pharmaceuticals in various engineering,
    development and commercial positions.</div>

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    </div>

  </div>

  <div><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;"><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>

  <div><br/>
  </div>

  <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>

  <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;">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>

  <div><br/>
  </div>

  <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;"><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;"><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>

  <div><br/>
  </div>

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

  <div style="text-align: justify;"><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;"><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;"><br/>
  </div>

  <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;"><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 Legal Officer, General Counsel and Corporate Secretary</div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><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>

  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">EUGENE SCHNEIDER, M.D.</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;">Executive Vice President, Chief Clinical Development and Operations Officer</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Schneider has served as Ionis&#8217; Executive Vice President and Chief Clinical Development and Operations Officer since September 2023.
    From January 2021 to September 2023, Dr. Schneider served as our Executive Vice President and Chief Clinical Development Officer. 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>

  <div><br/>
  </div>

  <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;"><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, Research</div>

  <div><br/>
  </div>

  <div>
    <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>

  </div>

  <div><br/>
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item1A"><!--Anchor--></a>Item 1A. RISK FACTORS</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;">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>

  <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 Commercialization of our Medicines</div>

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

  </div>

  <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 continue 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>

  <div><br/>
  </div>

  <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 will have to continue 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 continue 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>

  <div><br/>
  </div>

  <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 our commercial medicines and our medicines in development, we are not likely to
    generate substantial revenues or become consistently profitable.</div>

  <div><br/>
  </div>

  <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>

  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 our commercial medicines and our medicines in development, economically unviable. If the pricing of any of our medicines decreases for any
    reason, it will reduce our revenue for such medicine. For example, Biogen has in the past disclosed that SPINRAZA revenue decreased in part due to lower pricing in the U.S. and certain rest-of-world markets.</div>

  <div><br/>
  </div>

  <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 our commercial medicines and our medicines in development, depends upon a
    number of factors, including the:</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;">receipt and scope of 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;">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>
        </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;">cost and effectiveness of our medicines compared to other available therapies;</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;">patient convenience of the dosing regimen 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;">reimbursement policies of government and third-party payers.</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;">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 or our partners may develop.</div>

  <div><br/>
  </div>

  <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 and is available in the U.S. only through a risk evaluation and
    mitigation strategy, or REMS program. In addition, the product label for TEGSEDI in the U.S. has a boxed warning for thrombocytopenia and glomerulonephritis. Our main external 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.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; 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 our commercial
    medicines and our medicines in development, our revenue will 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 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, our commercial medicines and our medicines in development will face competition from other therapies and medicines for limited financial
    resources. Furthermore, 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. In addition, third-party payers may never consider our future products as cost-effective and 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>

  <div><br/>
  </div>

  <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>

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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;">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 (including by enhancing support for generic and biosimilar drugs), lower out-of-pocket drug costs for
      patients, curtail spread pricing practices by pharmacy benefit managers, and foster scientific innovation to promote better health care and improved health. In addition, the Inflation Reduction Act of 2022, or the IRA, 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. Specifically, in an effort to curb Medicare patients&#8217; out-of-pocket costs
      for prescription drugs, the Part D redesign legislation under the IRA requires, among other things, (1) </span>a cap on out-of-pocket drug spending under Part D, (2) drug manufacturers to pay a rebate to the federal government if prices for drugs
    covered under Part D and Part B increase faster than the rate of inflation, and (3) drug<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> manufacturers to contribute to the catastrophic coverage phase for Part D drugs as
      discounts through a manufacturer discount program. The IRA permits HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years. These provisions take effect progressively starting in fiscal year 2023.
      On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges. In response to the Biden administration&#8217;s
      October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve
      quality of care. It is unclear whether the models will be utilized in any health reform measures in the future. Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs using march-in
      rights under the Bayh-Dole Act. On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the
      price of a product as one factor an agency can use when deciding to exercise march-in rights. While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework. It is unclear whether or how these
      selected models or similar policy initiatives will impact prescription drug pricing in the future.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 covered entities under the Public Health Service Act 340B drug pricing program. 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;">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. For example, on January 5, 2024, the FDA approved Florida&#8217;s Section 804 Importation Program, or SIP, proposal to import certain drugs from Canada for specific state healthcare programs. It is unclear how this
    program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada. Other states have also submitted SIP proposals that are pending review by the FDA. Any such approved
    importation plans, when implemented, may result in lower drug prices for products covered by those programs. 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>

  <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 compete effectively, our medicines, including our commercial medicines and our medicines in development,
    will not generate significant revenues.</div>

  <div><br/>
  </div>

  <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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    <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;">priced lower than our medicines;</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;">reimbursed more favorably by government and other third-party payers than our medicines;</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;">safer than our medicines;</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;">more effective than our medicines; 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;">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 our commercial medicines and our medicines in development, obsolete or
    non-competitive.</div>

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  <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 our commercial medicines 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;">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/>
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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;">Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;</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;">Taldefgrobep alfa, Evrysdi + GYM329 and NMD670 could compete with SPINRAZA;</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;">Patisiran, tafamidis, tafamidis meglumine and vutrisiran compete with TEGSEDI and WAINUA;</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;">Acoramidis, NTLA-2001 and NNC6019-0001 could compete with TEGSEDI and WAINUA;</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;">ARO-APOC3 and pegozafermin could compete with WAYLIVRA and olezarsen;</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;">Lanadelumab-flyo, C1 esterase inhibitor, berotralstat, C1 esterase inhibitor subcutaneous,
              garadacimab, </span>deucrictibant,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160; NTLA-2002 and STAR-0215 could compete with donidalorsen;</span></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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Olpasiran, </span>zerlasiran, lepodisiran and muvalaplin <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">could compete with pelacarsen;</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;">NI-005/AP-101 could compete with QALSODY;</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;">VIR-2218 + PEG-IFN-&#945;, VIR-3434 &#177; VIR-2218 &#177; PEG-IFN-&#945;, VIR-2218 + BRII-179, NI-204VIR-2218 + GS-9688 + nivolumab, AB-729, imdusiran + Peg-IFNa-2&#945; + NA, xalnesiran +
            RG6084 + NA, xalnesiran + NA, xalnesiran + pegIFN + NA, xalnesiran + RO7049389 + NA, xalnesiran + ruzotolimod + NA, RO7049389 + ruzotolimod + NA could complete with bepirovirsen; 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;">Budesonide, sparsentan, atrasentan, iptacopan, zigakibart, sibeprenlimab, atacicept, ravulizumab, vemircopan, felzartamab, povetacicept, avacincaptad pegol,
            pegcetacoplan, tinlarebant, danicopan, GT005, AVD-104 and ANX007 could compete with IONIS-FB-L<sub>Rx</sub>.</div>
        </td>

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</table>
  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><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 in the past disclosed that SPINRAZA revenue decreased 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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</span>.</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 our commercial medicines 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;">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>

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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 the U.S., TEGSEDI&#8217;s label contains a boxed warning for thrombocytopenia and glomerulonephritis;</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;">TEGSEDI requires periodic blood and urine monitoring; and</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;">in the U.S., TEGSEDI is available only through a REMS program.</div>
        </td>

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    </div>

  </div>

  <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
    regulatory authorities 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 CMOs 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 collaborations with Biogen for the development and commercialization of SPINRAZA and QALSODY.</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 separate collaborative arrangements with Biogen to develop and commercialize SPINRAZA and QALSODY. We entered into
    these collaborations primarily to:</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;">fund our development activities for SPINRAZA and QALSODY;</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;">seek and obtain regulatory approvals for SPINRAZA and QALSODY; and</div>
        </td>

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</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;">successfully commercialize SPINRAZA and QALSODY.</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 and QALSODY, generate additional clinical data for
    SPINRAZA and QALSODY, manufacture SPINRAZA and QALSODY, and successfully commercialize SPINRAZA and QALSODY. In general, we cannot control the amount and timing of resources that Biogen devotes to our collaborations. If Biogen fails to further develop
    SPINRAZA or QALSODY, obtain additional regulatory approvals for SPINRAZA or QALSODY, manufacture SPINRAZA or QALSODY, or successfully commercialize SPINRAZA or QALSODY, or if Biogen&#8217;s efforts in any of these respects are ineffective, revenues for
    SPINRAZA or QALSODY 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 collaborations with Biogen may not continue for various reasons. Biogen can terminate our collaborations at any time. If
    Biogen stops developing or commercializing SPINRAZA or QALSODY, we would have to seek or spend additional funding, and SPINRAZA&#8217;s or QALSODY&#8217;s commercialization may be harmed.</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 WAINUA.</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 WAINUA. Under the terms of the
    collaboration agreement, we and AstraZeneca will co-develop and co-commercialize WAINUA in the U.S. and AstraZeneca will have the sole right to commercialize WAINUA in all other countries. 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 WAINUA is not successful
    for any reason, WAINUA may not meet our commercial objectives and our revenues for WAINUA 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 WAINUA 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 WAINUA.</div>

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    </div>

  </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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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. While</span> we believe <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">our current capabilities and those we obtain through third-party manufacturers support our
      manufacturing needs now, it will be important to expand our manufacturing infrastructure in the future, which will likely require substantial expenditures. 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.</span></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 our commercial medicines and our medicines in development, or could result in enforcement action after authorization that might limit the commercial success of our
    medicines, including our commercial medicines 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 WAINUA and drug product for WAYLIVRA.
    Any delays or disruption to our own or third-party commercial manufacturing capabilities could limit the commercial success of our medicines.</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 our commercial medicines, 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 our commercial medicines 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>

  <div><br/>
  </div>

  <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 authorities will not approve our medicines for marketing or our commercial medicines in additional markets or for additional indications. If the FDA or another regulatory authority believes that we or our partners have not sufficiently
    demonstrated the safety or efficacy of any of our medicines, including our commercial medicines or our medicines in development, the authority 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 Notice of Non-Compliance Withdrawal Letter, or Non-W, from Health Canada for WAYLIVRA in
    November 2018.</div>

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    </div>

  </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>

  <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;">such authorities may disagree with the design or implementation of our clinical studies;</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;">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>

  </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;">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>
        </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;">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>

  </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;">such authorities may disagree with the interpretation of data from preclinical or clinical studies;</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;">such authorities may find deficiencies in the manufacturing processes or facilities of third-party manufacturers who manufacture clinical and commercial supplies for our
            medicines; 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 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>
        </td>

  </tr>


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

  <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 in development, or failure to receive additional marketing authorizations for
    our commercial medicines, 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;">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 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.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 QALSODY did not meet the primary clinical endpoint in the Phase 3 VALOR study; however, trends favoring QALSODY 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.</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 factors that could cause a clinical study to fail or be delayed, including:</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;">the clinical study may produce negative or inconclusive results;</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;">regulators may require that we hold, suspend or terminate clinical research for noncompliance with regulatory requirements;</div>
        </td>

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</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, 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>
        </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 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>

  </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 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>

  </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 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 or 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>

  </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 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>

  </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 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>
        </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 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>

  </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 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>

  </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 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>

  </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 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>

  </tr>


</table>
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Further, the FDA or other regulatory authorities 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. In addition, under accelerated approval the FDA is requiring completion of the
    ongoing Phase 3 trial for QALSODY to confirm the clinical benefit of QALSODY.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Moreover, our commercial medicines 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. Any failure or delay in our clinical studies 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 WAINUA for the treatment of ATTR-CM, donidalorsen, olezarsen, ulefnersen and zilganersen. 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 have in the past experienced labor shortages, which impacted their ability to perform services for us for certain of our clinical trials. Subsequent failures of these third parties to carry out their obligations, or a termination of our
    relationship with such third parties, could delay or prevent the development, marketing authorization and commercialization of our medicines.</div>

  <div><br/>
  </div>

  <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 or Gaza, we do have a limited number of clinical trial sites in
    Russia and Israel that may be materially impacted by the ongoing wars between Russia and Ukraine and military conflicts in Israel and the surrounding areas, as well as related political or economic responses and counter-responses by various global
    actors, or collectively, conflicts in Eastern Europe and the Middle East, 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>

  <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;">AstraZeneca for the joint development and funding of WAINUA;</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;">Novartis for development and funding of pelacarsen;</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;">GSK for development and funding of bepirovirsen; 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;">Roche for development and funding of IONIS-FB-L<sub>Rx</sub>.</div>
        </td>

  </tr>


</table>
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    </div>

  </div>

  <div><br/>
  </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>

  <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;">conduct clinical studies;</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 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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</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;">manufacture and commercialize 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;">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, Otsuka 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, Otsuka or Roche, could determine that it is in its financial
    interest to:</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;">pursue alternative technologies or develop alternative products that may be competitive with the medicine that is part of the collaboration with us;</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;">pursue higher-priority programs or change the focus of its own development programs; 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;">choose to devote fewer resources to our medicines than it does to its own 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;">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 QALSODY, SPINRAZA, WAINUA, bepirovirsen, donidalorsen, IONIS-FB-L<sub>Rx</sub> and pelacarsen.</div>

  <div><br/>
  </div>

  <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><br/>
  </div>

  <div style="text-align: justify; text-indent: 40.8pt; 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 olezarsen for the treatment of patients with FCS, to ulefnersen for the treatment of patients with FUS-ALS, and to ION582
    for the treatment of patients with Angelman syndrome. The FDA and EMA have granted orphan drug designation to WAINUA for the treatment of patients with ATTR, to donidalorsen for the treatment of patients with HAE, to TEGSEDI for the treatment of
    patients with ATTRv-PN, to WAYLIVRA for the treatment of patients with FCS, to tominersen for the treatment of patients with HD, and to ION356 for the treatment of patients with Pelizaeus-Merzbacher disease. 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>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </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 expansion of our manufacturing
    capabilities. All of these activities will require significant cash. As of December 31, 2023, we had cash, cash equivalents and short-term
    investments equal to $2.3 billion. If we or our partners do not meet our goals to successfully commercialize our medicines, including our
    commercial medicines, 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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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">successful commercialization of our commercial medicines;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the profile and launch timing of our medicines in development;</div>
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          <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>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">continued scientific progress in our research, drug discovery and development programs;</div>
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          <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>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the time and costs involved in obtaining marketing authorizations;</div>
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          <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>
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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;">our manufacturing requirements and capacity to fulfill such requirements.</div>
        </td>

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  <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, or commercial operations. 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 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, 2023, we had an accumulated deficit of approximately $1.8 billion and stockholders&#8217; equity of approximately $0.4
    billion. 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>

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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 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>

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  <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 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 our commercial medicines, 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 our commercial medicines or any of our medicines in
    development, it could have a material adverse impact on our business.</div>

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  <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/>
  </div>

  <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>

  <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>

  <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 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 our commercial medicines 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>

  <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 and that we recruit and retain qualified marketing, sales, market access, distribution, and related personnel to commercialize our medicines. We may not be able to attract and
      retain skilled and experienced personnel on acceptable terms because of intense competition for experienced personnel among many pharmaceutical and health care companies, universities and non-profit research institutions. In addition, failure to
      succeed in clinical studies or in commercializing our medicines may make it more challenging to recruit and retain qualified 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 pandemics, climate change and other events</div>

  <div><br/>
  </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, wars, 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;">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, enrollment in some of our clinical trials
    was delayed due to the COVID-19 pandemic.</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. We manufacture the finished drug product for TEGSEDI, WAINUA and WAYLIVRA at third-party contract manufacturers. Biogen manufactures the finished drug product for SPINRAZA and QALSODY. 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.</div>

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

  <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;">Risks related to cybersecurity, social media and artificial intelligence</div>

  <div><br/>
  </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>

  <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, particularly as companies (including us) moved to more remote work structures during and following 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 conflicts in Eastern Europe and the Middle East.</div>

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  </div>

  <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, delay progress on the development of our medicines, 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>

  <div><br/>
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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">The increasing use of social media platforms and artificial intelligence based software presents new risks and challenges.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Social media is increasingly being used to communicate about our medicines and the diseases our therapies are designed to treat. Social
    media practices in the biopharmaceutical industry continue to evolve and regulations relating to such use are not always clear and create uncertainty and risk of noncompliance with regulations applicable to our business. There is also a risk of
    inappropriate disclosure of sensitive information or negative or inaccurate posts or comments about us on social media. We may also encounter criticism on social media regarding our company, management, or medicines. Our reputation could be damaged by
    negative publicity or if adverse information concerning us is posted on social media platforms or similar mediums, which we may not be able to reverse. If any of these events were to occur or we otherwise fail to comply with applicable regulations, we
    could incur liability, face restrictive regulatory actions or incur other harm to 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;">Additionally, the use of artificial intelligence, or AI, based software is increasingly being used in the biopharmaceutical industry. Use
    of AI based software may lead to the release of confidential proprietary information, which may impact our ability to realize the benefit of our intellectual property.</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 securities and the global credit markets</div>

  <div><br/>
  </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. If we do not achieve milestones in accordance with our or our investors&#8217; or securities analysts&#8217; expectations, including milestones
    related to our commercial medicines and medicines in development, the price of our securities could decrease.</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;">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, 2023, the closing market price of our common stock ranged from $52.27 to
    $32.69 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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

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  </div>

  <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,
    recent events such as the COVID-19 pandemic, the ongoing conflicts in Eastern Europe and the Middle East, and the failure of Silicon Valley Bank have caused disruptions of global financial markets and resulted in increased volatility in the trading
    price of our common stock. 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, bylaws, convertible notes documents, call spread hedge transaction documents and Delaware
    law may prevent stockholders from receiving a premium for their shares.</div>

  <div><br/>
  </div>

  <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, chairperson 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;">In 2023, we completed a $575 million offering of 1.75% Notes and used $488.2 million of the net proceeds from the issuance of the 1.75%
    Notes to repurchase $504.4 million of our 0.125% Notes. In 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 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.</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>

  <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;">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, as of December 31, 2023, we may issue approximately 28.2 million shares of our common stock upon conversion of our
      1.75% Notes, 0% Notes and 0.125% Notes. In connection with the issuance of the 0% Notes and 0.125% Notes, we entered into certain call spread transactions covering 10.9 million shares and 6.6 million shares, respectively, </span>that we expect will
    <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">offset the dilution to holders of common stock upon any conversion </span>of those notes.&#160; In addition, o<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">f the shares reserved, 6.1 million shares are reserved for issuance upon conversion of 0.125% Notes that we have repurchased and are currently held by us in treasury (and thus would not be dilutive). As a result, to the extent we elect to
      convert the 0.125% Notes held by us in treasury, we expect we would receive up to 6.1 million shares upon settlement of related convertible note hedges (without any additional dilution caused by the conversion of the 0.125% Notes held in treasury).&#160;
      However, the anti-dilutive effect of the convertible note hedges is offset by certain warrant transactions we entered into in connection with the issuance of the 0% Notes and the 0.125% Notes. The addition of any of these shares into the public
      market may have an adverse effect on the price of our securities.</span></div>

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    </div>

  </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, financial
    condition or stock price.</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 and financial markets have experienced extreme volatility and disruptions recently, including as a result of the
    COVID-19 pandemic, ongoing conflicts in Eastern Europe and the Middle East, and the failure of Silicon Valley Bank. These disruptions can result in severely diminished liquidity and credit availability, declines in consumer confidence, declines in
    economic growth, increases in unemployment rates and uncertainty about economic stability. There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur. If the current equity
    and credit markets deteriorate, it may make any necessary debt or equity financing more difficult, more costly and more dilutive. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect
    on our operations, growth plans, financial performance or stock price. In addition, 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.</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;">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</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>

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          <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>

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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;">difficulties in staffing and managing foreign operations;</div>
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          <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: 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>

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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;">U.S. and foreign government tariffs, trade and export restrictions, price and exchange controls and other regulatory requirements;</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;">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: 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, in particular foreign
            countries or globally;</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;">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>
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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 tax, employment, privacy, immigration and labor laws, regulations and restrictions for employees living or traveling abroad;</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;">workforce uncertainty in countries where labor unrest is more common than in the U.S.; 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;">changes in diplomatic and trade relationships.</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 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 contract research organizations,
    contract manufacturing organizations, distributors, wholesalers, agents, contractors and other partners) will comply with anti-bribery laws. Importantly, 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.</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 compliance with laws</div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our operations are subject to extensive legal and regulatory requirements affecting the health care industry.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operations are subject to extensive legal and regulatory requirements affecting the health care industry, 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/>
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  <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>

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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 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>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">interruption of our research, development and manufacturing efforts;</div>
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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;">injury to our employees and others;</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;">environmental damage resulting in costly clean up; 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;">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>
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  <div><br/>
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  <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>

  </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 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 carry forward 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: justify; 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 our merger with Akcea Therapeutics, Inc. in
    2020, or 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
    NOLs 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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</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="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>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item1C"><!--Anchor--></a>Item 1C. Cybersecurity</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;">Risk management and strategy</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have implemented and maintain various information security processes designed to detect, respond to, recover, and protect our
    technology ecosystem from cybersecurity threats. These processes are designed to identify, assess, and manage material risks that may result from cybersecurity threats and apply to our critical technologies inclusive of networks, third party hosted
    services, communications systems, hardware, software, and critical data, including intellectual property and confidential information that is proprietary, strategic, or competitive in nature.</div>

  <div style="text-align: justify;"><br/>
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    </div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our Information Technology department, led by our Senior Vice President, Information Technology, helps to detect, respond to, and manage
    cybersecurity threats and risks by monitoring and evaluating our threat environment using various manual and automated tools in certain environments and systems and other methods including, for example:</div>

  <div style="text-align: justify;"><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>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">analyzing reports of certain threats and actors;</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;">conducting scans of the threat environment;</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;">evaluating our and our industry&#8217;s risk profile;</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;">evaluating certain threats reported to 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;">conducting internal and external audits;</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;">conducting threat assessments for certain internal and external threats; 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;">conducting vulnerability assessments to identify vulnerabilities.</div>
        </td>

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  <div style="text-align: left;"><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Depending on the environment and system, we have implemented and maintain various technical, physical, and organizational measures,
    processes, standards, and policies designed to manage and mitigate material risks from cybersecurity threats to our critical technologies, including, for example:</div>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">incident response plan;</div>
        </td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">disaster recovery/business continuity plans;</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;">risk assessments;</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;">encryption of certain data;</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;">network security and access controls for certain systems;</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;">physical security;</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;">asset management, tracking and disposal;</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;">systems monitoring; 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;">employee training.</div>
        </td>

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  </div>

  <div style="text-align: justify; text-indent: 36pt; margin-bottom: 6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our assessment and management of material risks from cybersecurity threats are integrated into the Company&#8217;s overall
    risk management processes. For example, cybersecurity risk is assessed as a component of the Company&#8217;s enterprise risk management program. In addition, we have developed a process whereby our senior management will evaluate material risks from
    cybersecurity threats against our overall business objectives and will report certain cybersecurity incidents to the Audit Committee of the Board of Directors, which evaluates our overall enterprise risk.</div>

  <div style="text-align: justify; text-indent: 36pt; margin-bottom: 6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use third-party service providers to perform various functions throughout our business, such as application
    providers and hosting companies. We use third-party service providers to assist us from time to time to identify, assess, and manage material risks from cybersecurity threats, including, for example, legal counsel, cybersecurity consultants,
    cybersecurity software providers, penetration testing firms, and forensic investigators.</div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For a description of the risks from cybersecurity threats that may materially affect the Company and how they may do so, see our risk
    factors under Part 1. Item 1A. Risk Factors in this Annual Report on Form 10-K, including the risk factor titled &#8220;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">We are dependent on information
      technology systems, infrastructure and data, which exposes us to data security risks</span>.&#8221;</div>

  <div style="text-align: justify;"><br/>
  </div>

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

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; margin-bottom: 6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our Board of Directors addresses the Company&#8217;s cybersecurity risk management as part of its general oversight
    function. The Audit Committee of the Board of Directors is responsible for overseeing the Company&#8217;s cybersecurity risk management processes, including oversight and mitigation of risks from cybersecurity threats.</div>

  <div style="text-align: justify; text-indent: 36pt; margin-bottom: 6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cybersecurity risk assessment and management processes are implemented and maintained by our Senior Vice
    President, Information Technology, who is an information technology professional with healthcare and digital certifications and has over 25 years of relevant experience, and other employees in our Information Technology department who are certified
    security professionals and have relevant experience.</div>

  <div style="text-align: justify; text-indent: 36pt; margin-bottom: 6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our Senior Vice President, Information Technology is responsible for hiring appropriate personnel, helping to
    integrate cybersecurity risk considerations into the Company&#8217;s overall risk management strategy, communicating key priorities to relevant personnel, helping prepare for cybersecurity incidents, approving cybersecurity processes, and reviewing security
    assessments and other security-related reports.</div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cybersecurity incident response plan is designed to escalate cybersecurity incidents, depending on the circumstances, to our senior
    management team and Audit Committee of the Board of Directors. As part of such process, the Audit Committee of the Board of Directors receives regular reports from our Senior Vice President, Information Technology concerning the Company&#8217;s significant
    cybersecurity threats and risks and the processes the Company has implemented to address them.</div>

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    </div>

  </div>

  <div style="text-align: left;"><a id="Item2"><!--Anchor--></a><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 15, 2024, the
    following are the primary facilities in which we operate:</div>

  <div><br/>
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  <tr>

    <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: 12.86%; 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;">Location</div>
        </td>

    <td style="width: 1.87%; 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; border-top: #000000 2px solid; 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: 12.86%; vertical-align: bottom; border-top: #000000 2px solid; 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: 1.87%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; border-top: #000000 2px solid; 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; border-top: #000000 2px solid; 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; border-top: #000000 2px solid; 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; border-top: #000000 2px solid; 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: 12.86%; 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: 1.87%; 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: 12.86%; 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: 1.87%; 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: 12.86%; 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: 1.87%; 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; 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: 12.86%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Boston, MA</div>
        </td>

    <td style="width: 1.87%; 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;">14,300</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;">2029</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;">One, five-year option to extend</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: 12.86%; 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: 1.87%; 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;">5,800</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;">2027</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;">None</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;">Warehouse facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.86%; 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: 1.87%; 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;">4,200</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;">2028</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: 12.86%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dublin, Ireland</div>
        </td>

    <td style="width: 1.87%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; border-bottom: #000000 2px solid; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,900</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;">2025</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;">None</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.86%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 1.87%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; border-top: #000000 2px solid; border-bottom: #000000 4px double; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">331,100</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;">&#160;</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>


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

  <div style="text-align: justify; 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. Refer to Part IV, Section 15, Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated
      Financial Statements</span> for details on real estate transactions.</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 11, <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 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;">67</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </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 15, 2024, there were approximately 476 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, 2018 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="642" height="543" src="image12.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, 2018 in stock or index, including reinvestment of dividends. Fiscal year ending December 31.</div>

  <div><br/>
  </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;">68</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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;"><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-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>

    <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-23</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>
        </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;">111.75</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;">104.59</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; 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;">56.29</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;">69.87</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;">93.58</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;">136.69</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;">198.10</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;">242.03</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;">163.28</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;">236.17</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;">125.11</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;">158.17</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;">158.20</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;">142.19</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;">148.72</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. Reserved</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, 2023, and our financial condition as of December 31, 2023.
    Refer to our 2022 Form 10-K for our results of operations for 2022 compared to 2021. 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, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk
      Factors</span>. 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, for three decades, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">we have invented medicines that we believe bring better futures to people with serious diseases. Today, as a pioneer in RNA-targeted medicines, we continue to drive innovation in RNA therapies.</span> We currently have five
    marketed medicines: SPINRAZA, QALSODY, WAINUA, TEGSEDI and WAYLIVRA. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We also have a rich innovative late- and mid-stage pipeline in neurology, cardiology and other areas of
      high patient need. We currently have nine medicines in Phase 3 development and multiple additional medicines in early and mid-stage development</span>. 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 2023 compared to 2022. Refer to our 2022 Form 10-K for our results of operations for 2022 compared to 2021. The following table provides selected summary information from our consolidated statements of operations for 2023 and 2022 (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;">2023</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;">2022</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;">787.6</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;">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>

  </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;">1,141.4</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">
          <div style="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>

  </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;">(353.7</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;">(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>

  </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;">(366.3</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;">(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>

  </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;">2,331.2</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;">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>

  </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;">69</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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-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 2023 was $787.6 million compared to $587.4 million in 2022 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;">2023</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;">2022</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;">240.4</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;">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>

  </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;">Other 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">&#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: -18pt; 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%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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;">34.9</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;">30.1</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: -18pt; 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;" 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;">33.3</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;">31.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </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;">Total other commercial 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;">68.2</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;">61.1</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;">308.6</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;">303.4</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;">125.3</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;">68.6</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; 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;">100.5</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;">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>

  </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;">116.8</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;">37.0</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;">10.0</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;">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>

  </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;">352.6</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;">207.2</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%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA 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;">126.4</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;">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>

  </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;">479.0</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;">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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 99pt; 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;">787.6</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;">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>

  </tr>


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

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenues in 2023 were relatively consistent compared to 2022. Commercial revenue for 2023 included $240 million from SPINRAZA
    royalties, which were relatively consistent compared to 2022. Our commercial revenue in 2023 also included royalties from QALSODY U.S. product sales.</div>

  <div style="text-align: justify; text-indent: 36pt;"><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 increased in 2023 compared to 2022 primarily due to continued success with our pipeline and technology. As a result,
    we earned significant partner payments, including $50 million from AstraZeneca for the FDA approval of WAINUA for ATTRv-PN in the U.S., $36 million from AstraZeneca for licensing ION826 and payments from our new collaborations with Otsuka, Roche and
    Novartis.</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;">WAINUA (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 years ended December 31, 2023 and 2022 reflected the cost-sharing provisions related to our collaboration with AstraZeneca to develop and
    commercialize WAINUA 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.</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 WAINUA 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. We expect our medical affairs and commercialization expenses to increase as WAINUA 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 table sets forth information on revenue and expenses under this collaboration (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;">2023</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;">2022</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;">WAINUA joint 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">
          <div style="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;">126.4</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;">76.8</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: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development expenses related to Phase 3 development expenses for WAINUA</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;">150.8</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;">147.1</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;">Medical affairs expenses for WAINUA</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;">4.1</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;">2.0</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;">Commercialization expenses for WAINUA</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;">15.6</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;">2.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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;">70</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our WAINUA joint development revenue in 2023 includes a $50 million milestone payment from AstraZeneca that we earned when the FDA
    approved WAINUA for ATTRv-PN in 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; 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;">The following table sets forth information on operating 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;">2023</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;">2022</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;">1,035.7</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">
          <div style="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>

  </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;">105.7</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;">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>

  </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;">1,141.4</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;">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>

  </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 2023 compared to 2022, primarily
    due to certain one-time costs, including a non-cash charge associated with a lease exit and the license fee we paid to Vect-Horus. Our R&amp;D expenses increased as we advanced our pipeline, which included an increase in the costs associated with our
    clinical studies as most of our Phase 3 studies were either fully enrolled or approaching full enrollment at the end of 2023. Our SG&amp;A expenses increased due to expenses related to our launch preparation activities for WAINUA, olezarsen and
    donidalorsen.</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;">The following table sets forth information on cost of sales (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;">2023</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;">2022</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;">8.7</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">
          <div style="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>

  </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;">0.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <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>

  </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;">9.1</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;">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>

  </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; 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, medical affairs, 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;">2023</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;">2022</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;">821.7</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">
          <div style="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>

  </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;">77.9</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;">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>

  </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;">899.6</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;">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>

  </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;">71</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </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;">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;">The following table sets forth information on drug discovery 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;">2023</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;">2022</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;">125.6</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;">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>

  </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;">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>

  </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;">141.8</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>

    <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>

  </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, decreased in 2023 compared to 2022. In 2022, we
    recognized $80 million for licensing Metagenomi&#8217;s gene editing technologies.</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;">2023</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;">2022</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;">WAINUA</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;">115.5</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;">103.9</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;">TEGSEDI and WAYLIVRA</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;">8.1</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;">10.6</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: -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;">138.3</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;">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>

  </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;">24.9</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;">14.1</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;">Zilganersen</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;">5.6</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%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ulefnersen</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;">10.8</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;">8.4</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: 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%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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;">101.0</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;">123.5</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;">Development overhead 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;">123.3</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;">92.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </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;">530.3</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;">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>

  </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;">34.5</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;">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>

  </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;">564.8</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>

    <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>

  </tr>


</table>
  <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 2023 compared to 2022 primarily
    due to our advancing late-stage pipeline and full or nearly full enrollment of many of our Phase 3 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. 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 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;">72</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </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;">Our medical affairs function is responsible for funding and coordinating investigator-sponsored trials, communicating scientific and
    clinical information to healthcare providers, medical professionals and patients, and managing publications.</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 medical affairs 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;">2023</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;">2022</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;">19.5</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;">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>

  </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;">3.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <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>

  </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;">22.9</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;">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>

  </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 2023 compared to 2022 as we continued advancing 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, validation batches to support regulatory approvals, 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;">The following table sets forth information on manufacturing and development chemistry 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;">2023</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;">2022</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;">65.3</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;">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>

  </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;">8.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <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>

  </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;">74.1</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;">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>

  </tr>


</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;">Manufacturing and development chemistry expenses, excluding
      non-cash compensation expense related to equity awards, decreased in 2023 compared to 2022. In 2022, we manufactured higher quantities of API to support launch preparation activities for WAINUA, 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, information technology 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;">2023</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;">2022</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;">27.2</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;">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>

  </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;">28.7</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;">19.2</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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consulting</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;">4.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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;">0.8</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: -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%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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;">4.3</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;">4.7</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;">Insurance</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;">3.6</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">&#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;">3.8</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;">Computer software and licenses</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;">2.7</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; 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;">9.7</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;">8.2</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;">81.0</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;">59.8</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;">15.0</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;">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>

  </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;">96.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <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>

  </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;">73</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <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 2023 compared to 2022. The
    increase was primarily related to increased occupancy, personnel and consulting 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;">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 SG&amp;A 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 and QALSODY.</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;">2023</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;">2022</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;">205.1</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">
          <div style="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>

  </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;">27.5</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;">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>

  </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;">232.6</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;">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>

  </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, increased in 2023 compared to 2022 primarily due to
    increased expenses related to our go-to-market activities for WAINUA, olezarsen and donidalorsen. In addition, we recorded a one-time expense of $20 million when we terminated a build-to-suit lease agreement in August 2023. Refer to Part IV, Item 15,
    Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the
      Consolidated Financial Statements</span> for further details on the lease termination<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;">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 2023
    was $89.0 million compared to $25.3
    million for 2022. The increase in investment income was primarily due to an increase in interest rates associated with our investments in debt
    securities and an increase in our cash available for investment during 2023 compared to 2022. Our cash balance increased due to the $500.0 million upfront payment we received in January 2023 from our royalty purchase agreement with Royalty Pharma
    Investments, or Royalty Pharma, net proceeds we received from the debt offering in June 2023 and payments from partners. These increases were partially offset by the repurchase of $504.4 million in principal of our 0.125% Notes during 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;">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;">2023</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;">2022</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 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;">5.9</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;">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;">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;">6.4</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;">0.7</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%; 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;">0.4</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;">2.1</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%; 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;">12.7</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;">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>

  </tr>


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

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2023, we completed a $575.0 million offering of our 1.75% Notes and repurchased $504.4 million in principal of our 0.125% Notes. As a
    result, beginning in the second quarter of 2023, our interest expense related to our convertible notes increased because we began incurring interest expense for our 1.75% 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;">74</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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; font-weight: bold;">Interest Expense Related to Sale of Future Royalties</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 recorded $</span>68.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of interest expense related to the sale of future royalties in 2023 as a result of the
      Royalty Pharma transaction, in which we sold a minority interest in our future SPINRAZA and pelacarsen royalties to Royalty Pharma for a $500 million upfront payment and $625 million of potential future payments. Refer to </span>Part IV, Item 15,
    Note 7, <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 the Consolidated Financial Statements<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for further details.</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;">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 $1.9 million and
    $7.3 million loss on investments for 2023 and 2022, respectively. The period-over-period fluctuation in our loss on investments was primarily
    driven by changes in the fair value of our investments in publicly traded and privately held biotechnology companies.</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 2022, we closed a purchase and sale agreement with a real estate investor in which we sold and leased back the facilities at our
    headquarters location in Carlsbad, California for a total purchase price of $263.4 million and recorded a gain of $150.1 million in 2022, resulting in income tax expense of $8.8 million. Refer to Part IV, Item 15, Note 7, <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 this transaction.</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 Income (Expense)</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 2023, we completed a $575.0 million offering of our 1.75%
      Notes and used $488.2 million of the net proceeds to repurchase $504.4 million in principal of our 0.125% Notes. As a result of these repurchases, we recorded a $13.4 million gain on early retirement of debt in 2023, which reflects the difference
      between the amounts we paid to repurchase portions of our 0.125% Notes and the net carrying balance of the liability at the time that we repurchased the debt. Refer to </span>Part IV, Item 15, Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated Financial Statements for further
      details regarding our convertible debt.</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;">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 $32.3 million for 2023 compared to $11.7 million for 2022.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The primary drivers of our income tax expense despite our full year pretax loss relate to the requirement for taxpayers to amortize
    research and development expenditures over five years pursuant to Internal Revenue Code, or IRC, Section 174 beginning in 2022 under the Tax Cuts and Jobs Act of 2017, or TCJA, and the impact of the royalty purchase agreement with Royalty Pharma, which
    we reflected as a taxable sale which required us to include the proceeds from the sale, net of currently deductible issuance costs, as taxable income in 2023. The resulting tax liability is partially offset by the utilization of our R&amp;D tax
    credits.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The increase in income tax expense for 2023 compared to 2022 relates primarily to the impact of the Royalty Pharma transaction.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We continue to maintain a full valuation allowance on all our net deferred tax assets.</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 $366.3
    million for 2023 compared to $269.7
    million for 2022. Our net loss increased for 2023 compared to 2022 primarily due to factors discussed in the sections above<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>Basic and diluted net loss per share for 2023 were $2.56 compared to $1.90 for 2022.</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;">75</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </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 financed our operations from commercial revenue from SPINRAZA and QALSODY royalties and TEGSEDI and WAYLIVRA commercial revenue. In addition, we expect to receive commercial revenue from WAINUA
    royalties beginning in 2024. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From our inception through December 31, </span>2023,
    we have earned approximately $7.2 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, the issuance of long-term debt and the sale of future royalties. From the time we were founded through </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have raised net proceeds of approximately $</span>2.1&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">billion from the sale of our equity securities. Additionally, from our inception through </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have borrowed approximately $</span>2.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion under long-term debt arrangements and received proceeds of $0.5
      billion from the sale of future royalties to finance a portion of our operations.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cash, cash equivalents and short-term investments, working capital and long-term obligations increased from 2022 to 2023. As discussed
    above, in 2023, we repurchased $504.4 million in principal of our 0.125% Notes. In the third quarter of 2023, we closed a real estate transaction and received $32.4 million. In the second quarter of 2023, we issued $575.0 million of 1.75% Notes (due in
    June 2028). In the first quarter of 2023, we received an upfront payment of $500.0 million when we entered into a royalty purchase agreement with Royalty Pharma and recorded a corresponding long-term liability related to the sale of future royalties.</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, excluding our liability related to the sale of future royalties, as of December 31, 2023. 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;">Part IV, Item 15, Note 7, </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 </span>Notes to the Consolidated Financial Statements<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;">1.75% Notes (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">
          <div style="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;">620.3</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;">10.1</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">
          <div style="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;">610.2</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;">0% Notes (principal 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;">632.5</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;">&#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: 9%;" 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%; 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;">0.125% Notes (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;">44.6</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">&#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;">44.6</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">&#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>

  </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;">Building mortgage payments (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;">10.2</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;">0.5</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;">9.7</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: 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;">Operating leases</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;">279.5</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;">20.4</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;">259.1</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: 64%; padding-bottom: 2px;">
          <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;" 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>

    <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;">0.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <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; 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;">1,587.9</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;">75.7</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;">1,512.2</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 contractual obligations consist primarily of our convertible debt. In addition, we also have a facility mortgage, facility leases,
    equipment financing arrangements and other obligations. We believe our cash, cash equivalents and short-term investments, as well as plans for cash in the future, will be sufficient to fund our planned operations and these obligations. We have not
    entered into, nor do we currently have, any off-balance sheet arrangements (as defined under SEC rules).</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 7, </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 the 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 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated
      Financial Statements</span> 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: 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 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated
      Financial Statements</span> 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>

  </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: 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 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 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated Financial Statements</span>
    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, 2023 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 which 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, securing lines of credit or executing royalty monetization agreements. 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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Part IV, Item 15, </span>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: 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;">Assessing the propriety of revenue recognition and associated deferred revenue;</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 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; 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 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 appropriate estimate of anticipated future royalty payments under our royalty purchase agreement</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>

  </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;">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/>
  </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;">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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  <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;">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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  <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;">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 amount of effort 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 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 a 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>);</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 a milestone payment relates to services we are performing or if our partner is performing the 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;">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;); 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;">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;">, </span>in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Notes to the Consolidated Financial Statements</span>&#160;<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>

  </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;">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, 2023, 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 $10.6 million.</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;">Liability Related to Sale of Future Royalties</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 to monetize a portion of our future SPINRAZA and
    pelacarsen royalties we are entitled to under our agreements with Biogen and Novartis, respectively. Under our agreement with Royalty Pharma, we calculate the liability related to the sale of future royalties, effective interest rate and the related
    interest expense using our current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the
    medicines. The amount that Royalty Pharma will receive under the agreement is based on sales of SPINRAZA, our currently commercialized medicine, and pelacarsen, a product candidate that is not currently commercialized. As such, the repayment amounts
    that we estimate related to projections of future pelacarsen revenues contain more subjective estimation which we believe could lead to larger changes in estimates in the future. If there is a material change in our estimate, we will prospectively
    adjust the effective interest rate and the related interest expense.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of future royalty
    payments, particularly those from Novartis for pelacarsen, and could result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the regulatory approval and commercial sales of
    pelacarsen, competing products or other significant events. These factors and other events or circumstances could result in reduced royalty payments from sales of pelacarsen, which would result in a reduction of our non-cash royalty revenue and
    non-cash interest expense over the life of the agreement. Conversely, if sales of pelacarsen are more than amounts we estimated, the non-cash royalty revenue and non-cash interest expense we record would be greater over the life of the arrangement.</div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">.</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 </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 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>

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    </div>

  </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, 2023.</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;"><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, 2023, 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, 2023.</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, 2023, 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>

  <div><br/>
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    </div>

  </div>

  <div><br/>
  </div>

  <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, 2023, 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, 2023, 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, 2023 and 2022, 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, 2023,
    and the related notes and our report dated February 21, 2024 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 21, 2024</div>

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    </div>

  </div>

  <div><br/>
  </div>

  <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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Trading Plans</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;">During the quarter ended December 31, 2023, our
    officers and directors (as defined in Rule 16a-1(f) under the Exchange Act), or Section 16 officers and directors, adopted or terminated contracts, instructions or written plans for the purchase or sale of our securities as noted in the table below.</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Contract, instruction or written plan intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) under the Exchange Act.</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8220;Non-Rule 10b5-1 trading arrangement&#8221; as defined in item 408(c) of Regulation S-K under the Exchange Act.</div>
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    <td style="width: 2.45%; vertical-align: bottom;" rowspan="2">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Action</div>
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    <td style="width: 2.14%; vertical-align: bottom;" rowspan="2">&#160;</td>

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

    <td style="width: 2.26%; vertical-align: bottom;" rowspan="2">&#160;</td>

    <td style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="3">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Trading Arrangement</div>
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    <td style="width: 2.14%; vertical-align: bottom;" rowspan="2">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Shares</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> to be Sold</div>
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    <td style="width: 2.45%; vertical-align: bottom;" rowspan="2">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration Date</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Rule 10b5-1*</div>
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    <td style="width: 9.47%; vertical-align: bottom; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonNumeric name="ecd:NonRule10b51ArrAdoptedFlag" id="Fact_c1c2e177e03f4cd98895b874e54eec96" contextRef="c20231001to20231231" format="ixt:fixed-false">Non-Rule 10b5-1</ix:nonNumeric>**</div>
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  <tr>

    <td style="width: 21.67%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="ecd:TrdArrIndName" id="Fact_4e89c45995cc4c32ab1f3768121dd09d" contextRef="c20231001to20231231">Joseph Wender</ix:nonNumeric>, <ix:nonNumeric name="ecd:TrdArrIndTitle" id="Fact_0f8ae89405c343b38734a3dc70fb566f" contextRef="c20231001to20231231">Board Member</ix:nonNumeric></div>
        </td>

    <td style="width: 2.45%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adoption</div>
        </td>

    <td style="width: 2.14%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 15.03%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
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        </td>

    <td style="width: 2.26%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="ecd:Rule10b51ArrAdoptedFlag" id="Fact_085e371429e24bf5b4c7a2c6e0f9daff" contextRef="c20231001to20231231" format="ixt:fixed-true">X</ix:nonNumeric></div>
        </td>

    <td style="width: 2.14%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.47%; vertical-align: top; border-top: #000000 2px solid; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 2.14%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.62%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ecd:TrdArrSecuritiesAggAvailAmt" id="Fact_ea1b960ab6c3459d82d4b0ff3d948f50" contextRef="c20231231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">104,079</ix:nonFraction></div>
        </td>

    <td style="width: 2.45%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 15%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_9190fcfa2d974e0a83a1d614c438f473">February 28, 2025</span></div>
        </td>

  </tr>


</table>
</ix:continuation></div>

  <div style="text-align: justify; text-indent: 36pt; 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;"><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, 2023<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 make all required disclosures regarding any amendments to, or waivers from,
    provisions of 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>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <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, 2023.</div>

  <div style="text-align: left;"><br/>
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; 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; white-space: nowrap;">
          <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-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,090,732</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; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.43</div>
        </td>

    <td style="width: 0.87%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 16.36%; vertical-align: bottom; border-top: #000000 2px solid; border-bottom: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,976,286</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;">14,090,732</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;">48.43</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;">9,976,286</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>

  <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;">(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, 386,792 were available for purchase under the ESPP as of December 31, 2023.</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 8, <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;Information Regarding the Board
    and Corporate Governance" and "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;"><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;"><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;"><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;"><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;"><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;"><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 style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <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>

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


  <tr>

    <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: 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: 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: 10pt;"><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: 10pt;"><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/874015/000114036119022393/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: #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_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: #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_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;">4.8</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/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: #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/874015/000119312521113586/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: #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/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;">4.11</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/874015/000119312523165273/d511748dex41.htm">Indenture, dated as of June 12, 2023, by and between the Registrant and U.S. Bank Trust Company, a National Association, as trustee, including Form of
              1.75 percent Global Note due in 2028</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 June 12, 2023 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;">10.1*</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/874015/000087401523000136/ex10-1.htm">Second 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 March 31, 2023 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;">10.2*</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/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: #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="exhibit10-3.htm">10.3</a></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;">Form of Indemnity Agreement entered into between the Registrant and its Directors and Executive Officers with related schedule</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;">10.4</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/874015/000087401518000047/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: #CCEEFF;" 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: #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/874015/000114036119005627/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;">10.6*</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/874015/000087401523000136/ex10-2.htm">Registrant's 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 Quarterly Report on Form 10-Q for the quarter ended March 31, 2023 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;">10.7<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;">
          <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/874015/000087401523000105/exhibit10-10.htm">Form of Option Agreement for Options 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 Annual Report on Form 10-K for the year ended December 31, 2022 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;">84</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
  </div>

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


  <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;">10.8*</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;" 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/874015/000087401523000136/ex10-3.htm">Forms of Restricted Stock Unit Grant Notice and 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 Quarterly Report on Form 10-Q for the quarter
              ended March 31, 2023 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;">10.9*</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: 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; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.10<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;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-13.htm">Form of Option Agreement under the 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 Annual Report on Form 10-K for the year ended December 31, 2022 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;">10.11<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;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-14.htm">Form of Time-Vested Restricted Stock Unit Agreement for Restricted Stock Units granted under the 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 Annual Report on Form 10-K for the year ended December 31, 2022 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: 2.23%; 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/874015/000087401522000079/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;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.13<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;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-16.htm">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</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, 2022 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;">10.14*</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_ex99-1.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;">
          <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/874015/000114036120030055/brhc10018560_ex99-2.htm">Form of Global Option Agreement 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;">, 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;">10.16*</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_ex99-3.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;">
          <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_ex99-4.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>, 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.</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/874015/000114036117028398/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;">
          <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/874015/000114036117028398/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; 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/874015/000087401523000105/exhibit10-24.htm">Purchase and Sale Agreement between Ionis Gazelle, LLC and 2850 2855 &amp; 2859 Gazelle Owner (DE) LLC dated as of October 20, 2022</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, 2022 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>

  <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/874015/000087401523000105/exhibit10-25.htm">Purchase and Sale Agreement between the Registrant and Oxford I Asset Management USA Inc. dated as of October 20, 2022</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, 2022 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>

  <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/874015/000087401523000186/ex10-2.htm">First Amendment dated June 15, 2023 to the Purchase and Sale Agreement by and between the Registrant and Oxford I Asset Management USA Inc. dated as of
              October 20, 2022</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 June 30, 2023 and incorporated herein by
            reference<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;">10.23</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/874015/000087401523000105/exhibit10-26.htm">Lease Agreement dated October 20, 2022 between the Registrant and 2850 2855 &amp; 2859 Gazelle Owner (DE) LLC,</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, 2022 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>

  <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;">10.24</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/874015/000087401523000209/ex10-2.htm">Amended and Restated Lease Agreement between the Registrant and Lots 21 &amp; 22 Owner (DE) LLC dated as of August 21, 2023</a>, filed as an exhibit to the
            Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 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) is the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>


</table>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">85</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
  </div>

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


  <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="exhibit10-25.htm">10.25</a></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;">First Amendment dated as of November 6, 2023 to Amended and Restated Lease Agreement between the Registrant and Lots 21 &amp; 22 Owner (DE) LLC dated
            as of August 21, 2023.</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;">10.26</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: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-27.htm">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</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, 2022 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: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.27</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/874015/000087401523000105/exhibit10-28.htm">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</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, 2022 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;">10.28</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: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401523000105/exhibit10-29.htm">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</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, 2022 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: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.29</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_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: #FFFFFF;">
          <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: #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: 10pt;"><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: #CCEEFF;">
          <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: #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/874015/000110465911044376/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: #FFFFFF;">
          <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: #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: 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_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: #CCEEFF;">
          <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: #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/874015/000114036114030549/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: #FFFFFF;">
          <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: #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: 10pt;"><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: #CCEEFF;">
          <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: #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/874015/000114036114030549/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: #FFFFFF;">
          <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: #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: 10pt;"><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: #CCEEFF;">
          <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: #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/874015/000087401516000118/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>


</table>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86</div>

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    <div class="BRPFPageBreak" style="page-break-after: always;">
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
  </div>

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


  <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;" colspan="2">&#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/874015/000087401519000130/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;">10.39</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;" 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/874015/000087401514000095/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;">10.40</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;" 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/874015/000087401514000095/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;">10.41</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;" 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/874015/000110465912034636/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>

  <tr>

    <td style="width: 7.75%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.42</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.03%; 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/874015/000114036115009498/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: 7.75%; vertical-align: top; background-color: #FFFFFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.43</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.03%; 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_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: 7.75%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.44</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.03%; 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/874015/000110465913081234/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: 7.75%; vertical-align: top; background-color: #FFFFFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.45</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.03%; 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/874015/000114036115009498/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: 7.75%; 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: 2.22%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.03%; 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/874015/000087401516000118/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: 7.75%; vertical-align: top; background-color: #FFFFFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.47</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.03%; 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_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: 7.75%; 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: 2.22%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.03%; 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/874015/000110465913060361/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 March 31, 2023 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>

  <tr>

    <td style="width: 7.75%; vertical-align: top; background-color: #FFFFFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.49</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.03%; 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/874015/000087401515000057/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: 7.75%; 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: 2.22%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.03%; 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_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>


</table>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">87</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
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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;">10.51</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90%; 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/874015/000087401515000082/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: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.52</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90%; 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_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: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.53</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90%; 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/874015/000087401519000045/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: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.54</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90%; 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/874015/000087401520000115/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>

  <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;">10.55</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90%; 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/874015/000087401521000056/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: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.56</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90%; 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: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.57</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90%; 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/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>, 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.</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;">10.58</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90%; 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/874015/000087401517000033/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: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.59</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90%; 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_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: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.60</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90%; 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;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.61</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90%; 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;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.62</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90%; 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/874015/000087401521000056/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;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.63</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90%; 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/874015/000087401519000045/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>


</table>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">88</div>

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    <div class="BRPFPageBreak" style="page-break-after: always;">
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    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
  </div>

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


  <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;">10.64</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90%; 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/874015/000087401522000148/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;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.65</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90%; 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;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.66</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90%; 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;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.67</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90%; 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>

  <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;">10.68</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90%; 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/874015/000087401523000209/ex10-1.htm">Collaboration and License Agreement by and between the Registrant and Novartis Pharma AG dated as of August 2, 2023</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, 2023 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;">10.69</div>
        </td>

    <td style="width: 2.22%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90%; 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/874015/000087401523000209/ex10-3.htm">Research, Development, and License Agreement by and among the Registrant, F. Hoffmann-La Roche Ltd., and Hoffmann-La Roche Inc. dated as of September 26, 2023</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, 2023 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;">10.70</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;" colspan="2">
          <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;">10.71</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;" 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/874015/000087401521000166/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;">10.72</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;" colspan="2">
          <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;">10.73</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;" colspan="2">
          <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;">10.74</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;" 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/874015/000087401523000186/ex10-1.htm">Amendment No. 3 dated April 27, 2023 to the Collaboration and License Agreement by and between the Registrant and BicycleTx Limited dated July 9, 2021</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 June 30, 2023 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;">10.75</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;" 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/874015/000087401521000166/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: #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;" 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/874015/000087401522000079/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>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">89</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

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    <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;">10.77</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/874015/000087401523000186/ex10-3.htm">Letter Agreement dated June 29, 2023 in reference to the Collaboration and License Agreement dated December 6, 2021 by and between Akcea Therapeutics, Inc.
              and AstraZeneca AB</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 June 30, 2023 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>

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    <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;">10.78</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/874015/000087401523000105/exhibit10-80.htm">Collaboration and License Agreement between the Registrant and Metagenomi, Inc. dated November 10, 2022</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, 2022 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>

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    <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;">10.79</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/874015/000087401523000105/exhibit10-81.htm">Royalty Purchase Agreement by and between the Registrant, Akcea Therapeutics, Inc. and Royalty Pharma Investments 2019 ICAV dated as of January 9, 2023</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, 2022 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>

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  <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="exhibit10-80.htm">10.80</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;">License Agreement by and between the Registrant and Otsuka Pharmaceuticals Co., LTD. dated as of December 15, 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>

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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;"><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: #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;">List of Subsidiaries for the Registrant.</div>
        </td>

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    <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="exhibit23-1.htm">23.1</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;">Consent of Independent Registered Public Accounting Firm.</div>
        </td>

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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;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#POWEROFATTORNEY">24.1</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;">Power of Attorney &#8211; Included on the signature page of this Annual Report on Form 10-K.</div>
        </td>

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    <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="exhibit31-1.htm">31.1</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;">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>

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    <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="exhibit31-2.htm">31.2</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 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>

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    <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="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: #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 Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.</div>
        </td>

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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;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit97.htm">97</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;">Registrant&#8217;s Amended and Restated Clawback Policy</div>
        </td>

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  <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, 2023, 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>

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    <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>

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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>
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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>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">90</div>

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    </div>

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  <div><br/>
  </div>

  <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;"><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 21<sup>st</sup> day of February, 2024.</div>

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    <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>

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  <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>

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    <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>

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    <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>

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  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="POWEROFATTORNEY"><!--Anchor--></a>POWER OF ATTORNEY</div>

  <div style="text-align: center;"><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>

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

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 21, 2024</div>
        </td>

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          <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>

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          <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>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 21, 2024</div>
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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>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Principal financial and accounting officer)</div>
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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;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Chairman of the Board</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 21, 2024</div>
        </td>

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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>
        </td>

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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>

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          <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 21, 2024</div>
        </td>

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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>
        </td>

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    <td style="width: 49.28%; vertical-align: top;">&#160;</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;">/s/ ALLENE M. DIAZ</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 21, 2024</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>

    <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 21, 2024</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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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ JOAN E. HERMAN</div>
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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 21, 2024</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>
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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 21, 2024</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: 2.22%; vertical-align: top;">&#160;</td>

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    <td style="width: 16.06%; 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>

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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 21, 2024</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>

    <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;">/s/ JOSEPH H. WENDER</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;">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 21, 2024</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;">/s/ MICHAEL YANG</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 21, 2024</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Michael Yang</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <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;">91</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

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

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><!--PROfilePageNumberReset%Num%1%%%--></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;"><br/>
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    <td style="width: 93.34%; vertical-align: bottom;"> </td>

    <td style="width: 6.66%; 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;">Page</div>
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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_7a81b6d922e9497d8d2a788e6d2c738f">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>
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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, 2023 and 2022</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>
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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, 2023, 2022 and 2021</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>
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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, 2023, 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-6</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="#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, 2023, 2022 and 2021</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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    <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="#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, 2023, 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-8</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="#Notes">Notes to the 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-9</div>
        </td>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-1</div>

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    </div>

  </div>

  <div><br/>
  </div>

  <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;"><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, 2023 and 2022, 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, 2023, 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, 2023 and 2022, and the results of its operations and its cash flows for each of the
    three years in the period ended December 31, 2023, 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, 2023, based on criteria established in Internal Control&#8212;Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework), and our report dated
    February 21, 2024 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 Matters</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The critical audit matters communicated below are matters arising from the current period audit of the financial statements that were communicated or
    required to be communicated to the audit committee and that: (1) relate to accounts or disclosures that are material to the financial statements and (2) involved our especially challenging, subjective or complex judgments. The communication of critical
    audit matters 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 matters below, providing separate opinions on the critical audit matters or on the
    accounts or disclosures to which they relate.</div>

  <div><br/>
  </div>

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    <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, 2023, the Company accrued $106 million for clinical development expenses. As discussed in Note 1 to the consolidated financial
            statements, the Company records costs for clinical trial activities based upon estimates of costs incurred through the balance sheet date that have yet to be invoiced related to third-party clinical management costs, laboratory and analysis
            costs, toxicology studies and investigator grants. The Company estimates its liability using assumptions about study and patient activities and the related expected expenses for those activities 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 and contract research organization 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>

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    </div>

  </div>

  <div><br/>
  </div>

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    <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 expenses. This included controls over management's assessment of the assumptions and accuracy of data underlying the accrued clinical development expenses 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 expenses, 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 expenses 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 expenses and compared the results
            to the current year accrual.</div>
        </td>

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    <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;">Accounting for the Royalty Pharma Sale of Future Royalties Transaction</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 discussed in Note 7 to the consolidated financial statements, in January 2023, the Company entered into a royalty purchase agreement to monetize a
            portion of future SPINRAZA and pelacarsen royalties that the Company is entitled to under existing agreements. As a result, the Company received an upfront payment of $500 million. The Company accounted for the sale of future royalties as a
            liability. The Company determines the effective interest rate used to record interest expense based on the estimate of future royalty payments over the term of the agreement. The carrying value of the liability related to the sale of future
            royalties at December 31, 2023 was $514 million.</div>
          <div>&#160;</div>
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Auditing the Company&#8217;s liability related to the sale of future royalties was complex due to the subjective judgments required to forecast the
            expected royalty payments subject to the agreement and due to the nature and extent of audit effort required to address these matters. Specifically, as it related to pelecarsen, a product candidate that is not currently commercialized, these
            estimates include significant assumptions such as market penetration, probability of success, and sales price, among others, that are affected by expectations about future market conditions.</div>
        </td>

  </tr>


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  <div><br/>
  </div>

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    <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: 81.74%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We obtained an understanding, evaluated the design, and tested the operating effectiveness of controls over the Company&#8217;s processes for estimating
            the amount and timing of future royalty payments.</div>
          <div style="text-align: justify;">&#160;</div>
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To test the liability balance and the amount of interest expense recognized, our audit procedures included, among others, evaluating the methodology
            used and assessing the significant assumptions and the underlying data used by the Company in its effective interest model. We compared the significant assumptions in the estimate of future royalty payments to current industry and market
            trends. We recalculated the current year interest expense based on the amortization schedules and estimates of royalties using the effective interest method, and performed sensitivity analyses to evaluate the changes in the effective interest
            rate, and associated interest expense, that would result from changes in the assumptions.</div>
        </td>

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  <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_82d859af1eba4fe8aee884f197aeaeea" contextRef="c20230101to20231231">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_38195236812643f6b0738807adcd2923" contextRef="c20230101to20231231">San Diego, California</ix:nonNumeric></div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 21, 2024</div>

  <div><br/>
  </div>

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    </div>

  </div>

  <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>

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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="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>

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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;">2023</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;">2022</div>
        </td>

    <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;">&#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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsAtCarryingValue" id="Fact_bc9174e7fd1b46998715a48e884958d3" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">399,266</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:CashAndCashEquivalentsAtCarryingValue" id="Fact_7d7f77575df24801aeb6d430b5e2aea9" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">276,472</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;">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 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>

  </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%;">
          <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>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; 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: -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%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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:OperatingLeaseRightOfUseAsset" id="Fact_43d399b97c864bdfb4e458934ee3a2dc" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">171,896</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%; 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;">Deposits and other 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAssetsNoncurrent" id="Fact_028d5e12b53d44efafc7fc6259a8c677" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">105,280</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>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total assets</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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        </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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: center; text-indent: -9pt; margin-left: 9pt; 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;">LIABILITIES AND
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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">&#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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">26,027</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="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>

  </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">
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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;">
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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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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;">
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            convertible senior notes, 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">
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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%;">
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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>

  </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: 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; 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:OtherLiabilitiesCurrent" id="Fact_a0238d8cc02543e9b5dae4ea5a8e530b" 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">&#160;</td>

  </tr>

  <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 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:LiabilitiesCurrent" id="Fact_6dd286ee152042f78be1fe86c4b53e7b" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">448,090</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:LiabilitiesCurrent" id="Fact_324dbdee5a4a42159831822bf6b85720" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">311,561</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;">Long-term 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:ContractWithCustomerLiabilityNoncurrent" id="Fact_e76b53d24abc4ce98f4c0bd7bb5c4ee7" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">241,184</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:ContractWithCustomerLiabilityNoncurrent" id="Fact_4f3a8b90ab234988bb31ecd484021c4b" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">287,768</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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e98bb13d1a764fbcbf96d28c5ad88df9" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_14c88effe74142f9850cba1949788e6c" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction></ix:nonFraction> percent</span>
            convertible senior notes, 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:ConvertibleDebtNoncurrent" id="Fact_7d16c92292564b2da8688629df93896f" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">562,285</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:ConvertibleDebtNoncurrent" id="Fact_6a45bae12acd45d388faff32181d6045" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" 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: left; 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_ae9dd0da53e84dbf8340a62ff383a364" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_690ac053752949ef83ff3483789bf494" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction> percent</span>
            convertible senior notes, 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:ConvertibleDebtNoncurrent" id="Fact_650338a147284507b3de78e599e965c3" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">625,380</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:ConvertibleDebtNoncurrent" id="Fact_9dbda525a6ca4d9286888b5f137d3a36" 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>

  </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;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fbcbb5c14f1c4c92b00d1b67673a23b3" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_0e067406dd6047c6b1bf34d7673216e6" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction> percent</span>
            convertible senior notes, 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:ConvertibleDebtNoncurrent" id="Fact_4eab47dc0a1d4b1c9a9acd7ab3519611" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" 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">
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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;">
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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">&#160;</td>

  </tr>

  <tr>

    <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>

    <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: rgb(204, 238, 255); padding-bottom: 2px;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermLoansFromBank" id="Fact_b1093c295a3e4d8980c112cd144aa095" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,973</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Liabilities" id="Fact_72e72fa97a344884ae45c7d1457d4c58" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,603,386</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:Liabilities" id="Fact_e80cd271efab4a4c8c3d5beb70de894b" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,960,989</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%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Common stock, $<span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockParOrStatedValuePerShare" id="Fact_633d3f736e2247d291880fed08c8de60" contextRef="c20221231" unitRef="U004" decimals="3" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockParOrStatedValuePerShare" id="Fact_3582d99df2904a4ab26bce510bf362eb" contextRef="c20231231" unitRef="U004" decimals="3" scale="0" format="ixt:num-dot-decimal">0.001</ix:nonFraction></ix:nonFraction></span>
            par value; <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_9a0912d45871495e9d5ffb48117b86ac" contextRef="c20221231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_7cf23bc0b3da4da3818fa69653f089c6" contextRef="c20231231" 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="c20231231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_83959e73ecef45b7bf3b111575f95c72" contextRef="c20231231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">144,340,526</ix:nonFraction></ix:nonFraction></span> and <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_ae85ba7613de4a38acdf354791b136fa" contextRef="c20221231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_2e7ea39c8d104a0ca5cf2a5f9cdbc016" contextRef="c20221231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">142,057,736</ix:nonFraction></ix:nonFraction></span> shares issued and outstanding at December 31,
            <span style="text-indent: 0pt;">2023</span> and December 31, <span style="text-indent: 0pt;">2022</span>,
            respectively</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:CommonStockValue" id="Fact_5f48063ae846417a85a50e82db398716" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">144</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:CommonStockValue" id="Fact_942a957fd1a642b4a9846b941b383984" contextRef="c20221231" 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%; 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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,215,098</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:AdditionalPaidInCapitalCommonStock" id="Fact_a0bd160ae16c4b96869235d0b1952ae3" 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>

  </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;">Accumulated other comprehensive 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:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_7f6094dad8014d18a90ab96ded5f7902" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,645</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:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_3e9ce1fe826144aea3422b89b11598b2" contextRef="c20221231" 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%; 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; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accumulated deficit</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:RetainedEarningsAccumulatedDeficit" id="Fact_6946ee9e730b46ca9324cbc783ed82e1" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,795,911</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:RetainedEarningsAccumulatedDeficit" id="Fact_37e824371589479e8ba1817b0f9ad53a" contextRef="c20221231" 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: 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: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total stockholders&#8217; equity</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:StockholdersEquity" id="Fact_b7ec74b146a64c65af3896e315b42d76" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">386,686</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:StockholdersEquity" id="Fact_05294b8f30334228880f67edf83e2f36" 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: 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: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total liabilities and stockholders&#8217; equity</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>
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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>

    <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;">F-4</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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>
        </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;">2023</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;">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>

    <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;">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>

    <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>

    <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="c20230101to20231231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">240,379</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="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_ac6e240eca5848d5badb78f0ca60c1a3" 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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: 8.85pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other commercial 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_2383678941074355b9d4925186d90ab3" contextRef="c20230101to20231231_ProductOrServiceAxis_OtherCommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">68,212</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_996fb45aa67445ee9671efa9e0f75169" contextRef="c20220101to20221231_ProductOrServiceAxis_OtherCommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,044</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_543c70da466649fab328153c0cb49da9" contextRef="c20210101to20211231_ProductOrServiceAxis_OtherCommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">74,619</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%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 17.75pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fd9bb6ab6005461abb18649530165b23" contextRef="c20230101to20231231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">308,591</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_22602d3c8dbb4cce84585819b2a51d20" contextRef="c20220101to20221231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">303,358</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_00a0f7dfe1fe42f2a3f0f34b4024aee6" contextRef="c20210101to20211231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">342,395</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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;">Research and development 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">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_1620967f6acc42749745d5ae96e21c91" contextRef="c20230101to20231231_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">352,657</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0b96d8115fb4483dbc8311aafd1be7ec" contextRef="c20220101to20221231_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">207,222</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e3059784aae44cb6910ec96b251c7c0c" contextRef="c20210101to20211231_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" 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%; 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;">WAINUA joint development revenue</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">
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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>

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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%; 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%; 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%;">
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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">&#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%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent</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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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;">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">
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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%; 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">
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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: 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%;">
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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%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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">
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  </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%;">
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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">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment income</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:InvestmentIncomeNet" id="Fact_8190f0450b994481b761b63a19fa2db0" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">89,041</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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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:InvestmentIncomeNet" id="Fact_4cafde1786854b4a831f3771fe519f13" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,044</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;">Interest 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:InterestExpense" id="Fact_47eb0551e96b4a789a0b721ce64eef0f" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,660</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>

    <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: 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 related to sale of future 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">&#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:InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_79795cca858d44bf9654f0863fef96cb" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">68,797</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="ions:InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_e5458972ecb8427dac11831e016da93c" 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="ions:InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_d985916eae984cf3a7294c6311bc4d0e" 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>

  </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;">Gain (loss) on 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">
          <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;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gain (loss) on sale of real estate 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:GainLossOnDispositionOfAssets1" id="Fact_c3a4479d5bc24c12bbb3654f2b59fba2" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">161</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:GainLossOnDispositionOfAssets1" id="Fact_1e981ccfec9e4e77bdb93b732ca6bb87" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">149,604</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>

  </tr>

  <tr>

    <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">
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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">
          <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">
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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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_d3bdd0f2404d4109ab52a26b4122517d" 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_abea68078429482298990eda2a273682" 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>

  </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="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,321</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="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_4e00bc85f9de44bc9fae3e310059dd54" 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>

  </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: 4px;">
          <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%; 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_eed2832b2f23443a8a7b6a11b3b5c8be" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">366,286</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_17fba83bb5c645feab5192b45331713f" 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_1b16a95e7fa948b78f84194e8da4f693" 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>

  </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: 4px;">
          <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;" 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:EarningsPerShareDiluted" id="Fact_f5d991f3a037439da834811b6b2c9680" contextRef="c20230101to20231231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_ad4c690aa177438c98b7e63bbcd61da7" contextRef="c20230101to20231231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">2.56</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">
          <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:EarningsPerShareDiluted" id="Fact_7cdec1311ca947dfbacb3efc23b5ef61" contextRef="c20220101to20221231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_2c847af7934d4aee8d1e75c8c45eaaed" 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; 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:EarningsPerShareDiluted" id="Fact_f8c8aa80739c448c87fb108a521d3b50" contextRef="c20210101to20211231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_dc69ad9fdaac456cb95135c896add9e4" contextRef="c20210101to20211231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.20</ix:nonFraction></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">
          <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; 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; 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:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_240816d0c41d4bb8946ce32d9ec238f1" contextRef="c20230101to20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_974483869c87424686f8a9d8ad9407f8" contextRef="c20230101to20231231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">143,190</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">&#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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_9344acea647e4a1f9b5346ba564f05a7" contextRef="c20220101to20221231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_57a007ce704b4b8e9d16bf5187758b1a" 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; 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_7447762242904f9289b584753a2591b0" contextRef="c20210101to20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_24585fd306204e04ac047eefaae344a7" 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; 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;">F-5</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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;">2023</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;">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>

    <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;">&#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: 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:NetIncomeLoss" id="Fact_ca9d6b6e811d4d90a3511939ceaffd35" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">366,286</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:NetIncomeLoss" id="Fact_0f152c7175c442d096186ccdac7163b8" 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:NetIncomeLoss" id="Fact_e9347ab362a94c8f9fec26b2321644a8" 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: 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 investments, 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_33ff3ee28c9b4c45b1a904711a9fffdb" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">24,484</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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_7ada2fcd89584f6e9d084b26c02bad37" 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%; 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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_48783ec4c4a4439782c377df7893c03c" contextRef="c20210101to20211231" 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>

  </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;">Currency translation adjustment</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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_0118d01a0fc0483d942b9e51407b4717" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">351</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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_e0cf23c629544136a3b19d99634a49a6" 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%; 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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_107faab7668f4901940b3c076c0c0ec6" 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%; 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: 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;">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:ComprehensiveIncomeNetOfTax" id="Fact_88990aa910f44465b514db16de1b6797" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">341,451</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:ComprehensiveIncomeNetOfTax" id="Fact_a94a014398884db3aad264a9afa0f0b9" 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; 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:ComprehensiveIncomeNetOfTax" id="Fact_952a61bbba0241e4b821f51c3f0cbaf0" 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%; padding-bottom: 4px; 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;">F-6</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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; white-space: nowrap;" 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>

  </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; white-space: nowrap;" 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; white-space: nowrap;" 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>

  </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; font-weight: bold;">Balance at December 31, <span style="text-indent: 0pt;">2020</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:SharesIssued" id="Fact_e117c0623dcf44afaffde41830ff31f2" contextRef="c20201231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">140,366</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:StockholdersEquity" id="Fact_c2ee42f06fe64835a05ef7841d2d5bee" contextRef="c20201231_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: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_61b12d938cc04bbd933859666c726023" 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%; 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:StockholdersEquity" id="Fact_761affc8eaf842578c2a954083f3e28b" 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%; 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:StockholdersEquity" id="Fact_7ce172fc43e84fe9a84cda9a4771f340" 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%; 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:StockholdersEquity" id="Fact_d7625d3c6da54d3c8303ca9e6db6c22e" 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%; 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;">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;">&#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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_b699b94c66764330a7a4dd60cfe07928" 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_031beff8601a4b50b1c41faf88b4db91" 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_2c8cd11420aa41ba8dbf194cc8c306a6" 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_ea199b5eabb5480b9369c6725c638c86" 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%; 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:NetIncomeLoss" id="Fact_4b17e4c7ddb948378b5dc3b978592c2a" 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%; 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; 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: 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">&#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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_75d5b0ba5ab74db081164c7c0d5bef1d" 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: 9%; 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_5516c0cfbea4489cb3f64b2e9a7d1954" 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: 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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  </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>

    <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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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">&#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;">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: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_33c2bd3994484ec6b6b889f9854125a2" 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%; 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_acdf70a2832b43b187cc28260d07701f" 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: 9%; 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="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: 9%; 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_36d702b809b6438bb9992520363072bc" 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%; 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;">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">
          <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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_b6b516ec2a1a4c95bb1bb111b51f1bae" 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_20351fe1e74d4a8d835f7aa3d5293abc" 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%; 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:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_e1a9be17fbcc49cba1b7e1a25a26dac4" 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_1181345bb43d4d29a15a990784ecb435" 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_7a82d3300c7241d5b4e1dbbb0ffc14b4" 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%; 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;">Purchase of note hedges</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>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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:AdjustmentsToAdditionalPaidInCapitalOther" id="Fact_f8a3565ed4904042bd98ff63e1c0a8fc" 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: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalOther" id="Fact_7e2649971bd049fa84f3af8df5ca17ea" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" 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%; 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:AdjustmentsToAdditionalPaidInCapitalOther" id="Fact_6c5c871e8c4a4a978a217009321a6a5e" 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: 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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  </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>

    <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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_16b471403f9c439e97677ad055ba8ea5" 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: 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_e83c73ef6e1a48cdab01607508691d45" 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_473acb72b50d46e2912b68388715952b" 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_48fe59c7a1864cbb84ddefd32b4f681e" 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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; 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: 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:SharesPaidForTaxWithholdingForShareBasedCompensation" id="Fact_0e67bea4443f4bae9cd5edccf41111cf" 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; 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_f50b55d8ef9e493a980de223ce83bd7e" 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; 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_b40696a2aa1a463aa588302783bc1c6e" 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; 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_aa8b717f16a8434fa7369d0393962f2b" 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; 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_2a82343fb6bd448db961d1d4323f0b11" 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; 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_fcc84a575d9e4bd697d6f06df79559df" 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; 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; 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;" 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:SharesIssued" id="Fact_60e0ac539c624466a7e961a5cda44d3a" 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; 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:StockholdersEquity" id="Fact_4b39284014b0418f90e000374da7580f" 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; 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:StockholdersEquity" id="Fact_6585fe6638524b79b937ab63b9db5d75" 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; 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:StockholdersEquity" id="Fact_d286f9a454bc438c8afed1012262b3ab" 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; 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:StockholdersEquity" id="Fact_2ff016c0f0f747c19ebd4bac48864260" 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; 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:StockholdersEquity" id="Fact_5fa68cfcb9f54851a4ae9660cdc60d85" 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; 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;">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: 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">&#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:NetIncomeLoss" id="Fact_48bf356e63ad4d97b55fa3ddcc9213c8" 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: 9%; 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="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: 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">
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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>

    <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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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">
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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">
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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;">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: 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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_4cbf169782bc4f10bde4c3ae85dc7111" 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: 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_1b676bb0a1ac4edbbeeb6734b3d8013f" 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: 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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_333a9818653b4dfaab93cbf0c5a77aaa" 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: 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_49356eab4b864e50ae114d9ec765e817" 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>

  </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;">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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_3e593fdd22684db1bfb738748b3da710" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,194</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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_dab94e77a69241fca2928b4487c653a8" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" 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%; 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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_e0f954339b0b486b8eb0622218c8430b" 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_f1f39c8f1962432e8fd6b5b78bfe0cf1" 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_ab997a8b7d4a4042ab48b4f20127f6b2" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,373</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: 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;">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: 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">&#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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_4769b7f8ea594366a73ab91db2a60fa9" 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: 9%; 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="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%; 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3719dc6e9f1b486dae7106b08772f201" 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: 9%; 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="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: 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%; 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation" id="Fact_4ae64fbea2b243829db015f863e1a525" 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; 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_bb0a6cb28ba64220b97554fd600a837f" 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; 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_b049e26291e240409287825db6851635" 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; 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_69a5b77d2ba2483884724f7deb4c0ae6" 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%; 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_cbfd3f29efe544d8b18e1d3d119b4122" 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; 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:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_06512793fca04aafad083ac0b4088b51" 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; 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; 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;">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:SharesIssued" id="Fact_dcb079e20cba446096baf2d275d36dd5" 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; 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:StockholdersEquity" id="Fact_d01227787819409c840436d67e7d48a3" 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; 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:StockholdersEquity" id="Fact_acc570beab1c44b1b82a54a05d599805" 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; 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:StockholdersEquity" id="Fact_23b29f4e087c4f1ca664c32300610294" 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; 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:StockholdersEquity" id="Fact_71c821501e124dbfa12ced3159be86a4" 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; 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:StockholdersEquity" id="Fact_b1711f8987654d248ea55f4d0db1c024" 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; 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;">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;">&#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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_833dc2d79f584f5cadd8fbb8afa29236" contextRef="c20230101to20231231_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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_688bec339ca64d21a9b56fd99f2a667e" contextRef="c20230101to20231231_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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_2c0f61fe913a4e9c87a2ecd4f94a7897" contextRef="c20230101to20231231_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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_3178904620f649fd815c50c1e7ed399f" contextRef="c20230101to20231231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">366,286</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:NetIncomeLoss" id="Fact_f243d5703018413db94848f32ca2937c" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">366,286</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: 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;">Change in unrealized gains, 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: 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">&#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:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_1d4ee35e2c024559a37a84c8318f1601" contextRef="c20230101to20231231_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: 9%; 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="c20230101to20231231_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: 9%; 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="c20230101to20231231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">24,484</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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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: 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>

    <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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_d7f12853e21647d092a6acdeb0554051" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">351</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: 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;">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: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_f1afec8973614c0eb1dd5708b75a9108" contextRef="c20230101to20231231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,283</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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_79cd8079c7af49b0831707cd41c93616" contextRef="c20230101to20231231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2</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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_36423d90c0f0466fa3cfc8226e7c20a1" contextRef="c20230101to20231231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,439</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:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_6a5d7bca0e5f47b58411c7c493d6112c" contextRef="c20230101to20231231_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: 9%; 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="c20230101to20231231_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: 9%; 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_1cd0654a7f644d5c832df55e95a5d431" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,441</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: 28%; padding-bottom: 2px;">
          <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%; 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;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3984b222032b4f89a6067a1a1115ba11" contextRef="c20230101to20231231_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: 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_aee075691688409a968dbc6bfaabb0b8" contextRef="c20230101to20231231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">105,809</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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_56cd8c22ed5544bbb6a31360f46ba604" contextRef="c20230101to20231231_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: 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3058a5ae36ca41e8bec4bc5d2b8cd05a" contextRef="c20230101to20231231_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: 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:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3ae1822c76c04a1992dde0883ff4a37c" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">105,809</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: 28%; 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;">2023</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:SharesIssued" id="Fact_1d1f0719541143f2ae5ac80a19fb4007" contextRef="c20231231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">144,341</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:StockholdersEquity" id="Fact_74064f8288c1486bb2496106d6fd8aa7" contextRef="c20231231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">144</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:StockholdersEquity" id="Fact_41e9cc98d38a41778cf6eb70280117c2" contextRef="c20231231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,215,098</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:StockholdersEquity" id="Fact_aced03aa44534069aacaa219a523b4fc" contextRef="c20231231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,645</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">
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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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          <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">
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  </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 style="text-align: center; font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> <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;">F-7</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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;">2023</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;">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>

    <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:NetIncomeLoss" id="Fact_74418700e541478eadc5aced379a124b" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">366,286</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:NetIncomeLoss" id="Fact_3fb9b4a0ea3c4f27a1399c4165b5801f" 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:NetIncomeLoss" id="Fact_39b8baae321b42f7a5f4fa01fd0016cc" 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: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to reconcile net loss to net cash provided by (used in) operating 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;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Depreciation</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:Depreciation" id="Fact_9783424161d0448dad5051ce77601a96" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,292</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:Depreciation" id="Fact_6e647886642547db938d5dd7ac6cb6ac" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,328</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:Depreciation" id="Fact_c043d99cc86a49da958b7b3be663c1e1" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,487</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 right-of-use operating lease 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:OperatingLeaseRightOfUseAssetAmortizationExpense" id="Fact_187fd18217c9402ba4a18dc3da990453" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,647</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="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_215c70afe4f549f890056ebd2c3be83f" 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>

  </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 other 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:AmortizationOfIntangibleAssets" id="Fact_c4419687fb464fe5bdc6e0d2984bef36" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,559</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="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_dfcf2be324b646d9bb90e538cfcfa5d7" 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>

  </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 (discount) 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="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,885</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="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">&#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">
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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: 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">&#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%;">
          <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">
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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;">Loss (gain) 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">
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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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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="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">
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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;">Loss (gain) on sale of real estate 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">
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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">
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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>

  </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 valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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  <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: 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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">&#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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerAsset" id="Fact_e61ccb4ba21a4ee397258365ed72f449" 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%; 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInInventories" id="Fact_085c28a5897b4fdc902bd3eb96b38cfe" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,392</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:IncreaseDecreaseInInventories" id="Fact_721b959345b1466b92ba324d3da7222a" 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%; 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;">Other current and long-term 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:IncreaseDecreaseInOtherOperatingAssets" id="Fact_864803efe0c94dcc8ef6304a526731c5" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">29,840</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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherOperatingAssets" id="Fact_6e52fd98d6cb4429b89f68777b6ce49d" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">877</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: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounts 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:IncreaseDecreaseInAccountsPayable" id="Fact_a2882fd1ebf24bd894bdd232be12bb88" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,119</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:IncreaseDecreaseInAccountsPayable" id="Fact_19037c392df44ffaa87bb0e8fa58cb64" 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInAccountsPayable" id="Fact_fdf8edb884a5467dbfa35ec370b22a73" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">6,000</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;">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="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">4,098</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:IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable" id="Fact_928bf4ded5484066ada8046ae256e5bd" 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">
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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="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,549</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="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_1610f4d30b0d484693cb2ccb1dd531cd" 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>

  </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">
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  </tr>

  <tr>

    <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">
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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>

  </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>

    <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">
          <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_39199cc3649f4be29630e4d9f60a5e3f" 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>

  </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;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchases of 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">&#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:PaymentsToAcquireAvailableForSaleSecuritiesDebt" id="Fact_e72b6b733f32469391537642ed9f915f" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,770,814</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:PaymentsToAcquireAvailableForSaleSecuritiesDebt" id="Fact_dade26c6f20f4b60a4feec4e181794e8" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,485,772</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:PaymentsToAcquireAvailableForSaleSecuritiesDebt" id="Fact_67fd6ba04f7343b8835d000a36955a72" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,124,193</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: 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>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_4c7538b4bbdc45c8b0632c5597958d34" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,584,676</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:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_38e7752c94b34c97a1435e616eb5db40" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">989,152</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:ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" id="Fact_80d5593638ef4ce1981649265ba744b9" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,344,185</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;">Purchases of property, plant and equipment</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:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_af7f2fbf99644b83883250b2765bc5ae" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">23,805</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:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_28d3f3d53dd04a84a5b65fcacb820e59" 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">
          <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:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_77a9b1f4ce9d4712ac162eef39cf7ca1" 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>

  </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="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">22</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:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_5136df84cb9e4b99b4b52d41a1ac8066" 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_efecf5285ea845a984a8c24b6cf68305" 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>

  </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:PaymentsToAcquireIntangibleAssets" id="Fact_c4ddbc47fdde42a994020ac78cea3e4d" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,206</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">&#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">
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  </tr>

  <tr>

    <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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsToAcquireOtherInvestments" id="Fact_80fc4ad369ea4266aa819342e5a274f3" contextRef="c20230101to20231231" 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%; 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:PaymentsToAcquireOtherInvestments" id="Fact_2dd3f9b1b98e487c90386a8b5c2e7dbd" contextRef="c20220101to20221231" 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%; 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:PaymentsToAcquireOtherInvestments" id="Fact_62fe3844a7e8414ea863aff8f888c1ce" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,185</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">
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        </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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInInvestingActivities" id="Fact_f34b0cc23b5d447c95919927abae52a5" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">214,127</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:NetCashProvidedByUsedInInvestingActivities" id="Fact_dc86ed420ba74326be5713c12aa09032" 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInInvestingActivities" id="Fact_25c5a36f9c66441bbadcb049e1be0f09" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">194,906</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%;">
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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">&#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;">Proceeds from equity, 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:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_9766979c83c547faaf9db39fd1ec8b13" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,442</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_e8614ff277e9476fabd71fcec8d4876c" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,373</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:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_847a8383a3104ae19857ffdfc7350136" 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>

  </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="c20230101to20231231" 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:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_4420366a0a5648d6bb96c8031145c0f8" 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_0355270d749349ec8d585f6e041767cc" 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>

  </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 issuance of <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4642a52ab9ce4907b39eed0ffa26c5a5" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</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_7342e63e918d42e191e29bcf117f5cad" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">575,000</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_0ab38c70948548d799fe504eea9c12a3" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" 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_a4033a50401741c1b05cb977f4ff0e47" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" 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;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ddada546cbad473ba22dd53a170408fc" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction> percent</span>
            convertible senior notes 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="us-gaap:PaymentsOfDebtIssuanceCosts" id="Fact_295ea68d59684798888a6f3e259aa649" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,175</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:PaymentsOfDebtIssuanceCosts" id="Fact_e6bf4f1d9a154dc792f7ba7e5860ef4f" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" 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:PaymentsOfDebtIssuanceCosts" id="Fact_df6265ad6ec44742b960a285ededbf09" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" 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;">
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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="ions:EarlyRepaymentOfConvertibleDebt" id="Fact_bce24ec93a514254bb0db77d90368439" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">487,943</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">&#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:EarlyRepaymentOfConvertibleDebt" id="Fact_a897212cc7e8443f830d7f6b6e72d342" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" 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: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EarlyRepaymentOfConvertibleDebt" id="Fact_db7407774a2f461aad00bf18db9cb32e" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" 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%;">
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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="ions:ProceedsFromSaleOfFutureRoyalties" id="Fact_95dc46bd905b48f89195b36692463284" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">500,000</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:ProceedsFromSaleOfFutureRoyalties" id="Fact_2cbd526918944d95bccd56b91ec7d500" 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:ProceedsFromSaleOfFutureRoyalties" id="Fact_1a1dbc0d5c5f44748accd5559b4e128b" 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>

  </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;">Payments of transaction costs related to sale of future 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">&#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:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_c0775a432b6c4ebbb38dcca09c33571d" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,434</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="ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_6f9e0cfc307a413ebd3938e230788a53" 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%; 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="ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_39edc9b6eae64a328dfef179b5346bcd" 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>

  </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 real estate transaction</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:ProceedsFromRealEstateTransaction" id="Fact_419677fa184d47dbad3d65cb9d24a606" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,352</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:ProceedsFromRealEstateTransaction" id="Fact_ede17d8747da49a599d2995e53ce2a8f" 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:ProceedsFromRealEstateTransaction" id="Fact_ac9726081ddf4ff78ce21581fac853e2" 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>

  </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_0d079cd08b754cbf8bc7cb0a19cc1e0c" 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="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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_03ab8d471d1e4c8daa6066ec97f4dae1" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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>

  </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;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_88fe65f6a6c246e597d52cf05e99f678" 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%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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:PaymentsOfDebtIssuanceCosts" id="Fact_c265ed167f6849ca802177191ecfe56c" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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:PaymentsOfDebtIssuanceCosts" id="Fact_71796689b9704e64b6e32c07bc23d966" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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:PaymentsOfDebtIssuanceCosts" id="Fact_373cff2ecd4749f3b5c73b03bbd03408" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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%; 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;">Repurchase of $<span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_95a799cef52a4e1c9d77fb5fd03af9b6" 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_2e259db4949541f1800cf1f8675e1fe1" 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%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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:EarlyRepaymentOfConvertibleDebt" id="Fact_f70e21188bee4251b7e0cbbbb128a467" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" 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:EarlyRepaymentOfConvertibleDebt" id="Fact_6722f632b63b4e149ad0befd18fb572f" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" 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:EarlyRepaymentOfConvertibleDebt" id="Fact_e0141e05b2864bfcbb8b085c229eafa2" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" 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%; 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 valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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:RepaymentsOfConvertibleDebt" id="Fact_fb52319bb3e343a28dfb4c8402b73d68" contextRef="c20230101to20231231" 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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:RepaymentsOfConvertibleDebt" id="Fact_e2c4d66efd61435abf43c876b223e173" contextRef="c20220101to20221231" 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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:RepaymentsOfConvertibleDebt" id="Fact_dd36882e10e44acb8407f7c404b6f7bb" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,967</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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        </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:ProceedsFromIssuanceOfWarrants" id="Fact_495d0e1c772f477aa4b69187144a2acc" contextRef="c20230101to20231231" 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: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfWarrants" id="Fact_fd3083678ca946bc8c04d46f0ed04911" 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:ProceedsFromIssuanceOfWarrants" id="Fact_6a2730d1fb4e46bfbf665ffb2a8cec4f" 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: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; 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: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsForHedgeFinancingActivities" id="Fact_93476033a0d54173bc9010c262c485d1" contextRef="c20230101to20231231" 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:PaymentsForHedgeFinancingActivities" id="Fact_f5757aa8a1b84931b13cb7b1821bd15a" 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="us-gaap:PaymentsForHedgeFinancingActivities" id="Fact_18ed7373cfed41688772a16bc1938cfc" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" 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: 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;">Principal payments on debt</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:RepaymentsOfSecuredDebt" id="Fact_588ad9a9626c41d3bf5f5e384b12775c" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">160</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:RepaymentsOfSecuredDebt" id="Fact_abc6a6e24b2d4210a3f01c96ac626cc1" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">50,686</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:RepaymentsOfSecuredDebt" id="Fact_bf3b3c7f48c1498882ec15e09ed05b04" 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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <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>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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:NetCashProvidedByUsedInFinancingActivities" id="Fact_f60764a062974ce7927a4f93e49247af" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">644,082</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:NetCashProvidedByUsedInFinancingActivities" id="Fact_8fe541f932de4397b19679cb15ea1ecb" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">55,295</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:NetCashProvidedByUsedInFinancingActivities" id="Fact_5f3ea28877314458b840e3b2bce60168" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">245,933</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;">Effects of exchange rates on cash</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:EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" id="Fact_2ec1c832e41e458a8982750d8144f458" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">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:EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" id="Fact_201de8e539e449168662647513f45f4a" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">418</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:EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" id="Fact_2388628900e84ed4b19c5a7414d37478" 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>

  </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 increase (decrease) in cash and cash equivalents</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:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_489978ad0a9b4acdb5c858892347ff39" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">122,794</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:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_323a2b839be44267a57618d86a42c961" 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%; 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:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_15eb19737eab4e538dc8c84af74c487a" 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%; 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;">Cash and cash equivalents at beginning of 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:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" id="Fact_07f0dd136aab4f3da006f1b408361fc2" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">276,472</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 valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; 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;" 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="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">
          <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>

    <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>

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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; 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">
          <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>

    <td valign="bottom" 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>

    <td valign="bottom" 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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  <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="c20230101to20231231" 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">
          <div style="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="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_5c855545977c46e98693fab1376c9200" 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>

  </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="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">172</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="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">
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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>


</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;">F-8</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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>

  <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;">1. Organization and Significant Accounting Policies</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;">In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;).</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;">Organization and Business Activity</div>
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<div style="text-align: justify; text-indent: 36pt;"><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 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>
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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><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 prepare our consolidated financial statements in conformity with accounting principles generally accepted in the United States, or
    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><br/>
  </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><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 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><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;">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><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 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 WAINUA 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 selling, general and administrative, or SG&amp;A, expense and research and development, or R&amp;D, expense,
    respectively.</div>
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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-weight: bold;"><span style="text-decoration: underline;">Steps to Recognize Revenue</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;">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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<div><br/>
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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 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>
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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;">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><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c76796430" continuedAt="Text_345bcd5e81c440389ac5ba7c8c76796431"><ix:continuation id="Text_148c1d6ca04a49e59b23efb1ee3eea6a16" continuedAt="Text_148c1d6ca04a49e59b23efb1ee3eea6a17">
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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;">We and our partner approved the contract and we are both committed to perform our obligations;</div>
        </td>

  </tr>


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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;">We have identified our rights, our partner&#8217;s rights and the payment terms;</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;">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>

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</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;">We believe collectability of the consideration is probable.</div>
        </td>

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</table>
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  <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;">F-9</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </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>
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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 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>
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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 may 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. When a partner exercises its option to license a
      medicine that was not previously determined to be a material right at the inception of the agreement 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.</div>
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<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;">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>

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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;">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 that 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 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>
    <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c76796451" continuedAt="Text_345bcd5e81c440389ac5ba7c8c76796452"><ix:continuation id="Text_148c1d6ca04a49e59b23efb1ee3eea6a37" continuedAt="Text_148c1d6ca04a49e59b23efb1ee3eea6a38">
<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><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 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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<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>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c76796456" continuedAt="Text_345bcd5e81c440389ac5ba7c8c76796457"><ix:continuation id="Text_148c1d6ca04a49e59b23efb1ee3eea6a42" continuedAt="Text_148c1d6ca04a49e59b23efb1ee3eea6a43">
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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 royalties we may receive from future product sales;</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;">Estimated contractual milestone payments we may receive;</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 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>

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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;">A discount rate.</div>
        </td>

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</table>
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  <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;">F-10</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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;">We typically estimate the selling price of 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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    <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>

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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 estimated cost of work we will perform;</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 estimated cost of work that we will contract with third parties to perform; and</div>
        </td>

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</table>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c76796467" continuedAt="Text_345bcd5e81c440389ac5ba7c8c76796468"><ix:continuation id="Text_148c1d6ca04a49e59b23efb1ee3eea6a53" continuedAt="Text_148c1d6ca04a49e59b23efb1ee3eea6a54">
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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 API we will use.</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;">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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    <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>


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  </div>
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  <div>
    <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c76796473" continuedAt="Text_345bcd5e81c440389ac5ba7c8c76796474"><ix:continuation id="Text_148c1d6ca04a49e59b23efb1ee3eea6a59" continuedAt="Text_148c1d6ca04a49e59b23efb1ee3eea6a60">
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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>

  <div>
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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;">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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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c76796476" continuedAt="Text_345bcd5e81c440389ac5ba7c8c76796477"><ix:continuation id="Text_148c1d6ca04a49e59b23efb1ee3eea6a62" continuedAt="Text_148c1d6ca04a49e59b23efb1ee3eea6a63">
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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 recognize royalty revenue 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.</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;">Under our distribution agreements with Swedish Orphan Biovitrum AB, or 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="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>
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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: 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>

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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;">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 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 class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-11</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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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</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;">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>
        </td>

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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 Note 4, <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: 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><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 of December 31, 2023,
    approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_10e7a43398a0499b9e7ce86d84750009" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_OneSignificantCustomerMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">87.8</ix:nonFraction> percent of our contracts receivables were from <ix:nonFraction name="ions:NumberOfSignificantCustomers" id="Fact_fa43dcb0b8ee41488642917fbbe8ac66" contextRef="c20230101to20231231" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> significant customer. As of December 31, 2022, approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_bb586f81c8674dd6b924c9686075aa5b" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember" 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_3f1c8550953d4fb1bbaac07917b18557" contextRef="c20220101to20221231" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction>
    significant customer.</div>
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<div><br/>
  </div>
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<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964109" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964110"><ix:nonNumeric name="us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" id="Text_11c759b68b4b4c4b94628fcf39b9e913" contextRef="c20230101to20231231" escape="true" continuedAt="Text_5fe1ed02ba1a473f998078e44b1dd7421">
<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><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;">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><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964113" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964114"><ix:nonNumeric name="us-gaap:RevenueRecognitionPolicyTextBlock" id="Text_4fad649cf4524327bf2658a3254aca30" contextRef="c20230101to20231231" escape="true" continuedAt="Text_c5bcef744e6f45358d2b00b10af643121">
<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>
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<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964115" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964116"><ix:continuation id="Text_c5bcef744e6f45358d2b00b10af643122">
<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, 2023 and 2022, we recognized $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_7a9ec3bea8ad464ca6e12c6aa16435cd" contextRef="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">78.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_ced6b030f6d146bb91eabbce81e6f413" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">73.5</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><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964117" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964118"><ix:nonNumeric name="us-gaap:CostOfSalesPolicyTextBlock" id="Text_7bb4849d286842ec8c69f3be8efe749c" contextRef="c20230101to20231231" escape="true" continuedAt="Text_a69b112b021f4d418858d2b989dfdcbf1">
<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><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;">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><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964121" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964122"><ix:nonNumeric name="us-gaap:ResearchAndDevelopmentExpensePolicy" id="Text_3a1d8d5acce046e6b43dae80c783423c" contextRef="c20230101to20231231" escape="true" continuedAt="Text_13137e827d3a4b80ae55e15173521b9a1">
<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><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964123" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964124"><ix:continuation id="Text_13137e827d3a4b80ae55e15173521b9a2">
<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 R&amp;D operations. We expense R&amp;D costs as we incur them. When we make payments for R&amp;D 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 R&amp;D expenses are costs associated with our partner agreements. In 2023, 2022 and 2021, patent expenses were $<ix:nonFraction name="ions:PatentExpenses" id="Fact_85866a721e84472989175bb6188f4c57" contextRef="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.3</ix:nonFraction> million, $<ix:nonFraction name="ions:PatentExpenses" id="Fact_a0ff596166e44c50ba79c8d446d1bb4e" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.7</ix:nonFraction> million and $<ix:nonFraction name="ions:PatentExpenses" id="Fact_18be9a3bed5e4b5a815b9ba827f8eb2d" contextRef="c20210101to20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.3</ix:nonFraction> million, respectively.</div>
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<div><br/>
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  <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;">F-12</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </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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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964126" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964127"><ix:continuation id="Text_4a30e90a20c14da1b455c47bfb01b73a1" continuedAt="Text_4a30e90a20c14da1b455c47bfb01b73a2">
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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 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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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964128" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964129"><ix:continuation id="Text_4a30e90a20c14da1b455c47bfb01b73a3" continuedAt="Text_4a30e90a20c14da1b455c47bfb01b73a4">
<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964129" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964130"><ix:continuation id="Text_4a30e90a20c14da1b455c47bfb01b73a4" continuedAt="Text_4a30e90a20c14da1b455c47bfb01b73a5">
<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>
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<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964131" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964132"><ix:continuation id="Text_4a30e90a20c14da1b455c47bfb01b73a6" continuedAt="Text_4a30e90a20c14da1b455c47bfb01b73a7">
<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>
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  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964133" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964134"><ix:continuation id="Text_4a30e90a20c14da1b455c47bfb01b73a8">
<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>
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<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964135" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964136"><ix:nonNumeric name="us-gaap:EarningsPerSharePolicyTextBlock" id="Text_47e97970a2d74b528c3d5e13d3b65bad" contextRef="c20230101to20231231" escape="true" continuedAt="Text_07dca4b4efa647bba9baa7f79cc002891">
<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>
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<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964137" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964138"><ix:continuation id="Text_07dca4b4efa647bba9baa7f79cc002892" continuedAt="Text_07dca4b4efa647bba9baa7f79cc002893">
<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_345bcd5e81c440389ac5ba7c8c767964138" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964139"><ix:continuation id="Text_07dca4b4efa647bba9baa7f79cc002893" continuedAt="Text_07dca4b4efa647bba9baa7f79cc002894">
<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964139" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964140"><ix:continuation id="Text_07dca4b4efa647bba9baa7f79cc002894" continuedAt="Text_07dca4b4efa647bba9baa7f79cc002895">
<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 our net loss by our weighted-average number of common shares outstanding during the
    period.</div>
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<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964141" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964142"><ix:continuation id="Text_07dca4b4efa647bba9baa7f79cc002896" continuedAt="Text_07dca4b4efa647bba9baa7f79cc002897">
<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/>
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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, 2023,
    2022 and 2021, 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 from the following would have had an anti-dilutive effect on net loss
    per share:</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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_73bfeee93f8546f5b370edd9f616a4d4" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5c056baf11664eb8bb1412c9ff380ed0" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f51d9adf928c4a84aaf14638a3b4ce14" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</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_769655fa2afc4791b0ea57ec99a02fed" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_27a4ad482c384321b81448144513139e" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_45c13a6875054757a3b79a207fb51a99" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</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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    <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="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8e8c26f5c9244588940e55bdaee73dca" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_270fcf1505694f01b837e6326d809bfd" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</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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    <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="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_eb796a9cff164893992d0656c18cb133" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b26c82d7992442ff96c5568ee51f49f2" contextRef="c20211231_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="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_d9312f49e9424c82bffc13bbc2944526" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6f2d97c4eb3c416a953a12543f2d88d9" contextRef="c20221231_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: 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="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_313a82c8d6674d4c8879cbc00534b803" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1f4d9d777dda40daac28b07c65d54061" contextRef="c20221231_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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    <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>
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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;">Unvested restricted stock units, or RSUs;</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;">Unvested performance restricted stock units, or PRSUs; 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;">Employee Stock Purchase Plan, or ESPP.</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 year ended December 31, 2023, common stock underlying the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_d78308e8178f4c7fb2b6e0190ad9d696" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction> percent convertible senior notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f6cbce7782c24a39bbae59169e6d3d51" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes, would also have had an
    anti-dilutive effect on net loss per share.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally as of December 31, 2023, 2022 and 2021, we had warrants related to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9057afb608164fb98053858e7e341077" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_61f06d3de65749b7bf0c95864e191180" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4e11693e52d74388b6ddbdd15f6ae68c" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction></ix:nonFraction>% Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c70e1c3405324e9a9775523fd3e3866f" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_bd13f09db3d54fbbbdaf98adb97cd598" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5607593758b2425c96658da021cfddf2" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction></ix:nonFraction>% 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: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-13</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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 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 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 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="c20230101to20231231_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_7790526b5c3648779a4130225f212db9" contextRef="c20230101to20231231_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 years ended
    December 31, 2023 and 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="c20230101to20231231_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="c20230101to20231231_AwardDateAxis_GrantedPriorToJune2020Member_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. RSUs we granted to our board of directors after June 2020 fully vest after <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_317dd58aff2644f5948252ec0ede060a" contextRef="c20230101to20231231_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 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 PRSUs we granted in 2020 through 2022, <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="c20230101to20231231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U006" 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="c20230101to20231231_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="c20230101to20231231_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="c20230101to20231231_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="c20230101to20231231_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_b8fc319755bc4ee498c93684446fe058" contextRef="c20230101to20231231_AwardDateAxis_Granted2020Through2022Member_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="c20230101to20231231_AwardDateAxis_Granted2020Through2022Member_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="c20230101to20231231_AwardDateAxis_Granted2020Through2022Member_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. These PRSU awards also included an alternative <ix:nonNumeric name="ions:TermOfAlternativePayoutMechanism" id="Fact_fdf8d7ca12a54802a6d105e91ca3499f" contextRef="c20230101to20231231_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric> payout mechanism, or the Alternative Calculation, under
    which we must calculate an alternative payout at the end of the final <ix:nonNumeric name="ions:MeasurementPeriodForAlternativePayoutMechanism" id="Fact_636cbb73122d4a6f801622ea77774c32" contextRef="c20230101to20231231_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric> measurement period assuming the only measurement period for all
    shares under the award was the <ix:nonNumeric name="ions:MeasurementPeriodForAlternativePayoutMechanism" id="Fact_61e2f6c38e124a9bbf993e2175105896" contextRef="c20230101to20231231_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric> period. If the Alternative Calculation is greater than payouts under the sum of the <ix:nonNumeric name="ions:MeasurementPeriodForAlternativePayoutMechanism" id="Fact_c56a304476f24fa4ae572f8c62dbc6be" contextRef="c20230101to20231231_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:durwordsen">three years</ix:nonNumeric>, then such PRSU award will pay out to achieve the number of shares payable under the Alternative Calculation.</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 PRSUs we granted in 2023, <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_5c153f144c1b492e8ca12ea3a0e6b759" contextRef="c20230101to20231231_AwardDateAxis_GrantedIn2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction> percent of the PRSUs may vest at the end of the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_8d3cd9d9420b469fa8ebee749aed8aa9" contextRef="c20230101to20231231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric> performance period
    based on our relative TSR as compared to a peer group of companies and as measured at the end of the performance period. Under the terms of the grants, <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" id="Fact_a77aae45c4ef4362ac6ed7f43a02f281" contextRef="c20230101to20231231_AwardDateAxis_GrantedIn2023Member_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_cef441d443044be391448d0eecd8a2b3" contextRef="c20230101to20231231_AwardDateAxis_GrantedIn2023Member_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_c5042a913c244bf085af7da30aab1dff" contextRef="c20230101to20231231_AwardDateAxis_GrantedIn2023Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">200</ix:nonFraction> percent of the target number depending on our relative TSR.</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 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 style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Note 8, <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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Concentration of Credit Risk</div>
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<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>
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<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964186" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964187"><ix:nonNumeric name="us-gaap:FairValueOfFinancialInstrumentsPolicy" id="Text_1c1a3fa5b06c4f8eb0d08a8a2d8e1c26" contextRef="c20230101to20231231" escape="true" continuedAt="Text_0258406b01fd4ecdba36235aafbd7d821">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value Measurements</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964187" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964188"><ix:continuation id="Text_0258406b01fd4ecdba36235aafbd7d821" continuedAt="Text_0258406b01fd4ecdba36235aafbd7d822">
<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964188" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964189"><ix:continuation id="Text_0258406b01fd4ecdba36235aafbd7d822" continuedAt="Text_0258406b01fd4ecdba36235aafbd7d823">
<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><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964190" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964191"><ix:continuation id="Text_0258406b01fd4ecdba36235aafbd7d824">
<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>
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<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964192" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964193"><ix:nonNumeric name="us-gaap:InvestmentPolicyTextBlock" id="Text_6331a27b92f04118a22313343e337534" contextRef="c20230101to20231231" escape="true" continuedAt="Text_28cee6bb95e84ccc81a1a9e57905286d1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, Cash Equivalents and Investments</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964193" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964194"><ix:continuation id="Text_28cee6bb95e84ccc81a1a9e57905286d1" continuedAt="Text_28cee6bb95e84ccc81a1a9e57905286d2">
<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964194" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964195"><ix:continuation id="Text_28cee6bb95e84ccc81a1a9e57905286d2" continuedAt="Text_28cee6bb95e84ccc81a1a9e57905286d3">
<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>
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<div><br/>
  </div>
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  <div>
    <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964196" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964197"><ix:continuation id="Text_28cee6bb95e84ccc81a1a9e57905286d4" continuedAt="Text_28cee6bb95e84ccc81a1a9e57905286d5">
<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 public and private biotechnology companies that we received as part
      of a technology license or partner agreement. At December 31, 2023, we held equity investments in <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_b448547c88c7434cbc329f97a4b3ea28" contextRef="c20231231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> publicly traded companies and <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_5091e6339b9e4e85943dd42b9d332383" contextRef="c20231231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">seven</ix:nonFraction> privately held companies.</div>
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  </div>
<div><ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964197" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964198"><ix:continuation id="Text_28cee6bb95e84ccc81a1a9e57905286d5" continuedAt="Text_28cee6bb95e84ccc81a1a9e57905286d6">
<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964198" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964199"><ix:continuation id="Text_28cee6bb95e84ccc81a1a9e57905286d6">
<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 publicly traded companies at their listed stock price. 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>
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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;">Inventories</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 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>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-15</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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;">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>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964206" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964207"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentPolicyTextBlock" id="Text_cdabff15346b44629390c82abd47c849" contextRef="c20230101to20231231" escape="true" continuedAt="Text_03bcfd2a7f81448e92bd1b65d08a398c1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
  </div>
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  <ix:continuation id="Text_345bcd5e81c440389ac5ba7c8c767964208" continuedAt="Text_345bcd5e81c440389ac5ba7c8c767964209"><ix:continuation id="Text_03bcfd2a7f81448e92bd1b65d08a398c2" continuedAt="Text_03bcfd2a7f81448e92bd1b65d08a398c3"><ix:nonNumeric name="ions:PropertyPlantAndEquipmentUsefulLivesTableTextBlock" id="Text_ae9ad73d07bb4b9c96c8b308b9a0cddb" contextRef="c20230101to20231231" escape="true" continuedAt="Text_509f526763bd4ddf962ff0c5efd55cc71">
<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 we determine as the following (in years):</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; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">


  <tr>

    <td style="width: 80.34%; vertical-align: bottom;"> </td>

    <td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Useful Lives</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; 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;">Computer software, laboratory, manufacturing and other equipment</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_b828ac0b40e9470bb076f1ca83c087f8" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember_RangeAxis_MinimumMember" format="ixt-sec:duryear">3</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_55512527b3f64093815e4719a3a9da7a" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember_RangeAxis_MaximumMember" format="ixt-sec:duryear">10</ix:nonNumeric></div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_d29ce71868244871b343b50d2485de0e" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember_RangeAxis_MinimumMember" format="ixt-sec:duryear">15</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_dc8025be6cc74cca855f74c2367e8b3f" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember_RangeAxis_MaximumMember" format="ixt-sec:duryear">40</ix:nonNumeric></div>
        </td>

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  <tr>

    <td style="width: 80.34%; 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;">Land improvements</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_ebc4b025a1eb42b69cfea73de031e5b1" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_LandImprovementsMember" format="ixt-sec:duryear">20</ix:nonNumeric></div>
        </td>

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    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_a08cac9f5411485898c11087f1bef572" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember_RangeAxis_MinimumMember" format="ixt-sec:duryear">5</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_bda92ab03ee44df391ef93ce2060a192" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember_RangeAxis_MaximumMember" format="ixt-sec:duryear">15</ix:nonNumeric></div>
        </td>

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  <tr>

    <td style="width: 80.34%; 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;">Furniture and fixtures</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_8596a99804394834b242d29ed1c6c554" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember_RangeAxis_MinimumMember" format="ixt-sec:duryear">5</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:PropertyPlantAndEquipmentUsefulLife" id="Fact_2dd75df24eaa415ab54d1ac7e3d92e45" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember_RangeAxis_MaximumMember" format="ixt-sec:duryear">10</ix:nonNumeric></div>
        </td>

  </tr>


</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: 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 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>
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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: 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, 2023, we
    had <ix:nonFraction name="ions:DebtInstrumentNumberOfConvertibleNotes" id="Fact_10f5114021fc4f5bb04196fe30354c8a" contextRef="c20231231" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> outstanding convertible senior notes, our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_0da40ce130a0427ca4507455e50f00de" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes, which mature in June 2028, our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_88cf15606ae648ba879a91ce9224095e" contextRef="c20231231_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="c20231231_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 Note 7, <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; 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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Liability Related to Sale of Future Royalties</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 Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. Refer to Note 7, <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 the agreement.</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 agreement with Royalty Pharma, we record upfront payments and milestone payments we receive from the sale of future royalties as
    a liability, net of transaction costs. We record royalty payments made to Royalty Pharma as a reduction of the liability or accrued interest and amortize the transaction costs over the estimated life of the royalty stream. We account for the associated
    interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense using our
    current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material
    change in our estimate, we will prospectively adjust the effective interest rate and the related interest expense.</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;">We operate 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.</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 2023, the Financial Accounting Standards Board, or FASB, issued updated guidance on segment reporting. The guidance requires
    public companies with a single reportable segment to provide all disclosures required under ASC 280, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Reporting</span>. In addition, the guidance
    requires public companies to include in interim reports all disclosures related to a reportable segment's profit or loss and assets that are currently required in annual reports. This update is effective for annual periods beginning after December 15,
    2023 and interim periods beginning after December 15, 2024. The guidance is applied on a retrospective basis for all periods presented in the financial statements, unless it is impracticable. Early adoption of this guidance is permitted. We currently
    plan to adopt the annual reporting requirements in our 2024 Annual Report on Form 10-K. We plan to adopt the interim reporting requirements in our Quarterly Report on Form 10-Q in the first quarter of 2025.</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 2023, the FASB issued updated guidance on income tax disclosures. The new guidance requires companies to provide additional
    disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions and unrecognized deferred tax
    liabilities. This update is effective for annual periods beginning after December 15, 2024. Early adoption of this guidance is permitted. We currently plan to adopt this guidance in our 2025 Annual Report on Form 10-K.</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>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-17</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

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<div><ix:nonNumeric name="us-gaap:SupplementalBalanceSheetDisclosuresTextBlock" id="Text_49076dbe5ad448cdb9a7bcb57a3d6075" contextRef="c20230101to20231231" escape="true" continuedAt="Text_8f0a926dfcda48729238ac0e52efc01f1">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2. Supplemental Financial Data</div>
</ix:nonNumeric>

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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventories</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 inventory consisted of the following (in thousands):</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;">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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  <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;">2023</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;">2022</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>

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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="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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>

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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 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>
        </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>

    <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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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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  <ix:continuation id="Text_8f0a926dfcda48729238ac0e52efc01f8" continuedAt="Text_8f0a926dfcda48729238ac0e52efc01f9">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>
</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;">Our property, plant and equipment consisted of the following (in thousands):</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>

    <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">
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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">
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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 style="background-color: #CCEEFF; vertical-align: bottom; white-space: nowrap; width: 76%;">
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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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  <tr>

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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%; 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>

  </tr>

  <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>

    <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">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_7f69b083e88341d0a10c7007be88479a" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">159,233</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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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_3f9477a2105042be8cc52f98c29cba1b" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">153,441</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;">
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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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment" id="Fact_f5a1f6ad7d4e4b6b8e9550921b213332" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">96,759</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">
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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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentNet" id="Fact_4007d53a89214452be36c3718789c2f6" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">62,474</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:PropertyPlantAndEquipmentNet" id="Fact_8455ab90089d4679b0ea871acfd5ffa0" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">65,725</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: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land</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:PropertyPlantAndEquipmentGross" id="Fact_c9348a3d1fce44199a8e4bed4478b232" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_LandMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,569</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:PropertyPlantAndEquipmentGross" id="Fact_d9ffdb0b4d834bedb849aa2a434edef4" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_LandMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,569</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; margin-left: 33.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;Total</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:PropertyPlantAndEquipmentNet" id="Fact_624e9fa15570492aa71339f6bd1dedf0" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">71,043</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:PropertyPlantAndEquipmentNet" id="Fact_90431cc0470047e4b4d48b3cd20bde96" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">74,294</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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</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_8f0a926dfcda48729238ac0e52efc01f14" continuedAt="Text_8f0a926dfcda48729238ac0e52efc01f15">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</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 accrued liabilities consisted of the following (in thousands):</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
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</ix:continuation></ix:continuation>
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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;">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>

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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;">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>

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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">
          <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">
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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: 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_99a4ffc78cea4ea79a97e34f63ad0e36" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,945</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">
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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="ions:AccruedCommercialExpensesCurrent" id="Fact_6e4c39c15d234eb09c433b9792328307" 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>

  </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_159ba94a17f648459aba5b5549ce591d" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">29,598</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_ec657cc584984d58a779e475cb9c827b" 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>

  </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 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_c527b3021abd4093a2c21fd084cef7d4" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">147,894</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_8efb348efdaa4293a28fe2308d0572ac" 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>

  </tr>


</table>
</ix:continuation></ix:continuation></div>

  <div style="text-align: left;"><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;">F-18</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:RevenueFromContractWithCustomerTextBlock" id="Text_8fa4a07991ac4286b221053dfdaeed02" contextRef="c20230101to20231231" escape="true" continuedAt="Text_f284e183bbb046db8d8e5aae6d287e521">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3. Revenues</div>
</ix:nonNumeric>

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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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">During the years ended December 31, </span>2023<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, our revenues were comprised of the following (in
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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="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;"> </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;">2023</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;">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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; 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>

    <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>

    <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: -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;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fa6507c61eec4896be131baaf9c56b33" contextRef="c20230101to20231231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">240,379</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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; 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_7fc25e4d7b6b4b3a9dcd1da1e35355ad" 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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other 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">&#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>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; 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%; 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>

    <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">&#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">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total other commercial 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>

    <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_abce38c33594412d8019826b48d13405" contextRef="c20220101to20221231_ProductOrServiceAxis_OtherCommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,044</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_92aefda929294c40b3af86706f147a59" contextRef="c20210101to20211231_ProductOrServiceAxis_OtherCommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">74,619</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: 18pt; 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;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_03d2e1039bc445dd8b498d1d003c480c" contextRef="c20230101to20231231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">308,591</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_d26daf2df3aa4029995f664eeaccb2e3" contextRef="c20220101to20221231_ProductOrServiceAxis_CommercialMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">303,358</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>

  </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%;">
          <div style="text-align: left; margin-left: 18pt; 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;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_3db699190a8b445a8ca1d0999f8e2da6" contextRef="c20230101to20231231_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">352,657</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_cbc82f7aa39b411d84cac00bbafaae53" contextRef="c20210101to20211231_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" 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%; 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; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA 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_d04c651ddd214f21b5d79968c12ce7df" contextRef="c20230101to20231231_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">126,399</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_92beb73be7ff41f484f6dd3f5c805c37" contextRef="c20220101to20221231_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" 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">
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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%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: 36pt; margin-left: 27pt; 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_89ebf294558547c785a5851eb6bc535d" contextRef="c20230101to20231231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">479,056</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">&#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_f450bd3dc7c449ff8f7096209c42ed1d" 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>

  </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: 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: 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_0fe1d38055094dcaa16865c239b63886" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">787,647</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e4607d0da0554ea281285854370d4b3c" 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: 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_52fe1890f7e84daf8e430adf09e21d37" 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: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</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="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">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 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. We earn royalty revenue on net sales of
    QALSODY which is included in Licensing and other royalty 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: 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We earn commercial revenue from TEGSEDI and WAYLIVRA sales
      under our distribution agreements with </span>Sobi<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In addition, we receive royalties from</span> PTC Therapeutics International Limited, or PTC, for TEGSEDI&#160; and WAYLIVRA
    sales. Refer to Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, for details on our commercialization partnerships with Sobi and PTC.</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;"><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="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 variable 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 payment to the
    transaction price.</div>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-19</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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 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 who 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="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">WAINUA (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 WAINUA
    for the treatment of transthyretin amyloidosis, or ATTR. We jointly developed and are preparing to commercialize WAINUA with AstraZeneca in the U.S. We initially granted AstraZeneca exclusive rights to commercialize WAINUA outside the U.S., except for
    certain Latin American countries. In July 2023, we expanded those rights to include Latin America. Under the terms of the agreement, we received a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6bb92631bcb24cecb14c1db01373726d" contextRef="c20210101to20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" 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 WAINUA collaboration under ASC 808 and identified <ix:nonFraction name="ions:NumberOfMaterialComponents" id="Fact_77244fc7a2e94cb79c8cbd4b24da3caa" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U010" 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_ba2c8e8b9b084f918923e87c66222bf9" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U011" 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_7a3ad0b9fdcd4f748e4e867ab2270c0c" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" 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_5e87322def9b4973aefbf130af9125cb" contextRef="c20230101to20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" 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 WAINUA 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: 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. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. Under our 2013 strategic neurology collaboration, Biogen developed QALSODY (tofersen), our medicine that received
    accelerated approval in the U.S. to treat patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS. In addition, we and Biogen are currently developing numerous other investigational medicines to treat neurodegenerative diseases,
    including medicines in development to treat people with amyotrophic lateral sclerosis, or ALS, SMA, Angelman Syndrome, or AS, Alzheimer&#8217;s disease, or AD, and Parkinson&#8217;s disease, or PD. 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, 2023, we
    have received nearly $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_06e533557dd645a0a293de69cd61db32" contextRef="c20231231_RangeAxis_MaximumMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">3.8</ix:nonFraction> billion from our Biogen collaborations, including payments to purchase our stock.</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 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, 2023<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="c20231231_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">2.1</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="c20231231_ProductOrServiceAxis_SpinrazaRoyaltiesMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.6</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="c20231231_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="c20230101to20231231_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="c20230101to20231231_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 2023, we entered into a royalty purchase agreement with Royalty Pharma in which Royalty Pharma receives <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_be81c80b7c244d9ab9c1fe3ba5d94592" contextRef="c20231231_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember" 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="c20231231_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember" 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="c20231231_ProductOrServiceAxis_SpinrazaMember" 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="c20231231_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember" 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="c20231231_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">550</ix:nonFraction> million, depending on the timing and occurrence of the U.S. Food and Drug Administration, or FDA, approval of pelacarsen, which Novartis is developing.
    Refer to Note 7, <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 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;">.</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;">At the commencement of this
      collaboration, we received a </span>$<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_d0f059efca0b4cb78eead790f4fa19ae" contextRef="c20170101to20171231_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 from Biogen. In </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2021</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Biogen
      exercised its option to license ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">306</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, a drug we
      discovered under this collaboration, for which </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">we earned a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7948382269be4b958cfc743393d71711" contextRef="c20210101to20211231_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. We recognized this payment as revenue in full because</span> Biogen had full use of the license without any continuing involvement from us. 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. <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 ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">306</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, 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_3e6911040e1d45c0b915ba4b62552c08" contextRef="c20231231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">555</ix:nonFraction> million if Biogen advances ION306, which is comprised of up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_1777f9042b9e450888607262dedee914" contextRef="c20231231_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="c20231231_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="c20231231_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="c20230101to20231231_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 from any product that Biogen successfully commercializes under this collaboration.</span> From inception through December 31, 2023, we received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_99913c01602a40f391a5d4b461296e90" contextRef="c20231231_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="c20231231_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; 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 2018, we and Biogen entered into a strategic collaboration
      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 </span><ix:nonNumeric name="ions:TermOfCollaborationAgreement" id="Fact_3d01100b8b54487eb5650d892b0313da" contextRef="c20230101to20231231_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 targets</span>. In most cases, Biogen will be responsible for conducting IND-enabling toxicology studies for the selected medicine. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen has 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;">At the commencement of this collaboration, <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;">For each medicine under this 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_2f951ae27bf24c158a5ad4a9872a7763" contextRef="c20231231_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="c20231231_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="c20231231_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="c20231231_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. </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="c20230101to20231231_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 from any product that Biogen successfully commercializes under this collaboration.</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. From inception through December 31, 2023, we have received nearly $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_da56d1dc03c24e66a27cff951a361cbb" contextRef="c20231231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.1</ix:nonFraction> billion in payments under this collaboration, including payments to purchase our stock. We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_2ccf74adb28c46398e26d42924be60cb" contextRef="c20231231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction> million if Biogen licenses a medicine<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;">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="U011" 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, 2023,
    we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_20ba18c7432f48b692b7d780c2e643aa" contextRef="c20231231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">623</ix:nonFraction> million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in upfront and milestone payments in
      the transaction price for our R&amp;D services performance obligation under this collaboration, including a $</span><ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_3f7c210dad714493961c539d0e6cfc20" contextRef="c20231001to20231231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment we achieved in the fourth quarter of 2023. This milestone payment did not create a new performance obligation because it is part of our original R&amp;D services
      performance obligation. Therefore, we included this amount 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 2013, we and Biogen entered into a 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. In
    most cases, we are 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 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.</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 currently advancing <ix:nonFraction name="ions:NumberOfMedicinesCurrentlyBeingAdvanced" id="Fact_eb09908f5c9a48cc93d43f56069f13ca" contextRef="c20231231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</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="c20231231_ProductOrServiceAxis_MedicinesForAmyotrophicLateralSclerosisMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U012" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> medicines for ALS (QALSODY and ION541) and <span style="-sec-ix-hidden:Fact_7b05dc571fcb46f8bbbe0db51a44d460">a</span>
    medicine for multiple system atrophy (ION464). In 2018, Biogen exercised its option to license QALSODY, our medicine that received accelerated approval in April 2023 from the FDA for the treatment of adult patients with SOD1-ALS. As a result, Biogen is
    responsible for global development, regulatory and commercialization activities and costs for QALSODY.</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="c20130101to20131231_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.</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 QALSODY, we are eligible to receive nearly $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_eefd3cb9a90b4fa3a6dc831f3fe7cd65" contextRef="c20231231_ProductOrServiceAxis_QalsodyMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">110</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_fa8f6d1964ae452fb00307f7bed58d7b" contextRef="c20231231_ProductOrServiceAxis_QalsodyMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction> million license fee we received when Biogen
    licensed QALSODY from us in 2018, $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_3fa5a47d30f3491ea00f26479e205e7d" contextRef="c20231231_ProductOrServiceAxis_QalsodyMember_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="c20231231_ProductOrServiceAxis_QalsodyMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">55</ix:nonFraction> million in regulatory milestone payments. In addition, we are eligible to receive tiered royalties ranging from <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_98729a30805846bb9dabbcaaa529fcb3" contextRef="c20230101to20231231_ProductOrServiceAxis_QalsodyMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">11</ix:nonFraction> percent to <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_d55656a65016424796e95d22a42233ac" contextRef="c20230101to20231231_ProductOrServiceAxis_QalsodyMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">15</ix:nonFraction> percent on net sales of QALSODY. We will achieve the next milestone
    payment for QALSODY of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_531e5e06da924c38a4eddf832276baff" contextRef="c20231231_ProductOrServiceAxis_QalsodyMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction> million if the European Medicines Agency, or EMA, approves Biogen&#8217;s Marketing Authorization Application, or MAA,
    filing of QALSODY.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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="c20231231_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="c20231231_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="c20231231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million in development milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" id="Fact_c1d1f25511534235862a7aa4449afd2d" contextRef="c20231231_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 product
    that Biogen successfully commercializes under this collaboration. From inception through December 31, 2023, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_43252364b31243cf9fe665618b7d0d4d" contextRef="c20231231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">325</ix:nonFraction> million in payments under our 2013 strategic neurology collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_482f8849faa84cc1bef9409883137c72" contextRef="c20231231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">70</ix:nonFraction> million if Biogen licenses 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 our 2013 strategic neurology collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_5f22f24c59d44580af822992d7804572" contextRef="c20130930_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U011" 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;"> R&amp;D 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 $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_8e6bac473c9a4873a7bb0e87fa0b76df" contextRef="c20201231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">145</ix:nonFraction> million in total payments in the transaction price for our R&amp;D services performance obligation.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under this collaboration, we have also generated additional
      payments that we concluded were not part of our R&amp;D services performance obligation. We recognized each of these payments in full in the respective period we generated the payment because we did not have any performance obligations for the
      respective payment. For example, in 2023, we earned a </span>$<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ba45cef284724211a7df8091311affbd" contextRef="c20230101to20231231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">16</ix:nonFraction>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">million








      milestone payment from Biogen when the FDA approved Biogen&#8217;s New Drug Application, or NDA, for QALSODY, which we recognized in full because we did not have any remaining 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="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 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 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>
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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_949ac3f224694ebabb8efe3dfc11ef81" contextRef="c20120101to20121231_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. For each program under this
      collaboration, we are eligible to receive up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_ccb933b83b604dc18741069989989a26" contextRef="c20231231_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 license fee of up to $</span><ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_65a29b4f1fe9475eb78e5fdc8b36bd30" contextRef="c20231231_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, up to $</span><ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_e20fa4064cdb413c915fe0a890c9479d" contextRef="c20231231_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 and up to $</span><ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_0925b0bf59c64d2da6aebf2c6a32d0eb" contextRef="c20231231_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, 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="U013" 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, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_7a4c67230f974ba9bfd049a2c63e615a" contextRef="c20231231_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">230</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration, including $</span><ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_ebfd938753694a20a31568e6f2cfa086" contextRef="c20230101to20231231_ProductOrServiceAxis_Ion582Member_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">39</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
      during 2023 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 $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_7bc80b0e8adf47ca8dd64914ace6d170" contextRef="c20231231_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;">&#160;</span>million if Biogen licenses ION582 under this collaboration.</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 commenced development for IONIS-MAPT<sub>Rx</sub> and ION582, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_887da203fe8045ee837985e41f2a08d8" contextRef="c20121231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> separate performance obligations as our development work for each medicine. 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 obligations. In 2022, we completed our R&amp;D services performance obligation for IONIS-MAPT<sub>Rx</sub>. From inception through December 31, 2023, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_65c25865c5cb46d88f766f99f72dcb07" contextRef="c20231231_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>. From inception through December 31, 2023, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_d1bba18036de42709d2f5299c922f1d3" contextRef="c20231231_ProductOrServiceAxis_Ion582Member_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">68</ix:nonFraction> million in milestone payments in the transaction price for our ION582 development performance obligation, including $<ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_3a724f70eaf14949bff5b3baa1e44e78" contextRef="c20230101to20231231_ProductOrServiceAxis_Ion582Member_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">39</ix:nonFraction> million in milestone payments we received from Biogen for advancing ION582 during 2023.</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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts):</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; 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;">2023</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;">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: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>
        </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_1fd9f9b2ff4242a8ba5d5dc97a5064da" contextRef="c20230101to20231231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">350,146</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_73c0a219d58348498ce8dc987fd9d27e" contextRef="c20220101to20221231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">366,696</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_542df45308ad4ee9a37c56efe7fa18d1" contextRef="c20210101to20211231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">428,784</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: 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_b18b889b350941048d2231c689a9f351" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">44</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_33938ec04f5e40b889d8fcae645d637a" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">62</ix:nonFraction></div>
        </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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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_6c809afdaa814005b1f6b0887bff71f2" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">53</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;"><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>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2022<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="c20231231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">307.4</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_35c30aecc55949b1afd1112082165450" 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, 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;">WAINUA (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 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for
    the treatment of ATTR. In December 2023, the FDA approved eplontersen with the brand name, WAINUA, in the U.S. for ATTRv-PN. We are jointly developing and commercializing WAINUA with AstraZeneca in the U.S. We initially granted AstraZeneca exclusive
    rights to commercialize WAINUA outside the U.S., except for certain Latin American countries. In July 2023, we expanded those rights to include 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;"><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 $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_79969c9a9b914450bc63737b97f2fd7e" contextRef="c20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">3.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion, which is comprised of a $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_9dd7d53c8eee485eacad6e97dffdd4c2" contextRef="c20210101to20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</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_fef99a2e30ae4cc88317e2f706b3a709" contextRef="c20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" 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 license fee, up to $</span><ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_7c6f989ad85b49c8b6bfede72712bef2" contextRef="c20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">485</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development and approval milestone payments and up to $</span><ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_062b2352c9f546cca5d16c63150ff4fa" contextRef="c20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">2.9</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in sales milestone payments. The agreement includes territory-specific development,
      commercial and medical affairs cost-sharing provisions. In addition, we are eligible to receive up to mid-</span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" id="Fact_0b4829fbe9d847069807a9be4cf64ebe" contextRef="c20230101to20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" 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;"> royalties for sales in the U.S. and tiered royalties ranging from mid to high teens for sales outside the U.S. From inception through </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received nearly $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_7469eb0249ca4ffcac8492eb70284535" contextRef="c20231231_RangeAxis_MaximumMember_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">360</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration. We will achieve the next payment of $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_3dd9ebb411124d3da7c0f18716150d0d" contextRef="c20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" 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 upon regulatory approval of WAINUA for ATTRv-PN in the EU 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;">We evaluated our WAINUA collaboration under ASC 808 and identified <ix:nonFraction name="ions:NumberOfMaterialComponents" id="Fact_d4f80df42eb24e19af6957ccd65c9827" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U010" 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_AstraZenecaCollaborationWainuaMember" unitRef="U011" 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_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment we received in 2021. In 2023, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_79e35c2309284a009d4d2169f9d0c3eb" contextRef="c20230101to20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction> million license fee payment when we licensed rights to Latin America for WAINUA to AstraZeneca. We recognized these payments in full because we did not have any remaining performance
    obligations after we delivered the licenses 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="c20230101to20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" 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="c20230101to20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" 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 WAINUA 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. In 2023, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5f460923a7ec4d5d89e967c94b57f904" contextRef="c20230101to20231231_ProductOrServiceAxis_AttrvPnMember_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">50</ix:nonFraction> million milestone payment when the FDA approved WAINUA for ATTRv-PN in the
    U.S. We recognized this milestone payment in full as joint development revenue because we did not have any remaining performance obligations related to the milestone payment.</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 WAINUA, we have a collaboration with AstraZeneca focused on discovering and developing treatments for
    cardiovascular, renal and metabolic diseases, which we formed in 2015. 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>
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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="c20231231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">3.4</ix:nonFraction> billion, which is comprised of a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_afe0e303f52c47de8fef2665adbb52f3" contextRef="c20150101to20151231_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="c20231231_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_c41eea94f6c04393af0bccfd93fed8b5" contextRef="c20231231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">865</ix:nonFraction> million
    in development milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_efb4704088a04a6e826d67ea5c2f326d" contextRef="c20231231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">2.2</ix:nonFraction> billion in regulatory 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, 2023, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_b46d3be360f94ea788b2b83ce6c73f6f" contextRef="c20231231_RangeAxis_MinimumMember_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" 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_2b949e7c63b941a3955f5c01227834d5" contextRef="c20231231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">10</ix:nonFraction> million if AstraZeneca advances a medicine under this collaboration<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></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;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_12852f4c3cee4a69b4f4fee5d29498e6" contextRef="c20150731_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U011" 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> 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="c20231231_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>
</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;">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 period we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. For example, in 2023, we earned a
    $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_4d1e5d003192488c85affd353eff20db" contextRef="c20230101to20231231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">36</ix:nonFraction> million payment when AstraZeneca licensed ION826 from us. We recognized this payment in full in 2023 because we did not have any remaining
    performance obligations after we delivered the license to AstraZeneca.</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;">During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with AstraZeneca (in thousands, 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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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</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;">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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          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with AstraZeneca</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="text-align: left; vertical-align: bottom; 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b4bc1487977543468f0c2592f732bfb0" contextRef="c20220101to20221231_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">79,160</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">
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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_6f993bce8b8f4c7aa2348aedba4438cf" contextRef="c20210101to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">254,591</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: 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 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_dd338796e71247f6bc131ed50f37ef36" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">13</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_aa247af696394bd6806e0b89dffcff91" 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>
        </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;">We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_b22d4dca96604e1cb60121e3c991236b" contextRef="c20231231_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_cfd27ca80d9f460e8f3e825d0b1607b2" contextRef="c20221231_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, 2023 and 2022.</div>
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<div><br/>
  </div>
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  <ix:continuation id="Text_7d58284b292a4a309b54f7c4276fc8bf102" continuedAt="Text_7d58284b292a4a309b54f7c4276fc8bf103">
<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><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 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. Upon initiating the collaboration, we received an upfront payment of $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_df9eb741d1a047928581ba9b172e1706" contextRef="c20100101to20101231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction>
    million. Under our collaboration, GSK is developing bepirovirsen for the treatment of chronic hepatitis B virus infection, or 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>
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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="c20231231_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="c20231231_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="c20231231_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="c20231231_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="c20231231_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 and commercializes
    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, 2023, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_80b40aad4e4f428d854cce06e968dea2" contextRef="c20231231_RangeAxis_MinimumMember_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">105</ix:nonFraction> million in an upfront payment and payments related to the HBV program.</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 completed our R&amp;D services performance obligations in 2015, therefore 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 2023, we earned a $</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment when GSK initiated a Phase 3 program of
      bepirovirsen. We recognized this milestone payment as R&amp;D revenue in full in 2023 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next payment of $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_7ef9cac4d3634dc28f74729428a263ab" contextRef="c20231231_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><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;">During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with GSK (in thousands, except percentage amounts):</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</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;">2022</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;">2021</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="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%;" 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_ff3be5276ecf4d51a2514c2feff18233" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></div>
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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_64cbaaeaf4c249c28f7644f151cd8a75" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></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: 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="c20221231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_59e8ee0b0973416987e4c07862acaea5" contextRef="c20231231_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, 2023 and 2022.</div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-25</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Novartis</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;">Pelacarsen 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;">In 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 that Novartis initiated in 2019.</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_34bc42390fa34a3d9908bf5db5ae8531" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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="c20170101to20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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="c20231231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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="c20231231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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="c20231231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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="c20231231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">360</ix:nonFraction> million in sales milestone payments. We are also eligible to receive tiered royalties in the mid-teens to low <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_016f76af44eb49289c02150198f2a523" contextRef="c20230101to20231231_ProductOrServiceAxis_PelacarsenActivePharmaceuticalIngredientMember_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent range on net sales of pelacarsen. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_f70b581c4c184bd7afb533f20dd7fa6d" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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. We</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> will achieve the next payment of $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_3b19b0a102744ca58f85eea2983e6a84" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">50</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if the FDA accepts an NDA filing for pelacarsen.</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 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="c20170101to20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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="c20170101to20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">100</ix:nonFraction>
    million in 2017.</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_45dfae68b384426d9e7f35800c5ee5da" contextRef="c20170331_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> separate performance obligations:</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;">R&amp;D services for pelacarsen;</div>
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</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;">R&amp;D services for olezarsen;</div>
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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>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">API for pelacarsen; and</div>
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</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;">API for olezarsen.</div>
        </td>

  </tr>


</table>
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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 determined that the R&amp;D services for each medicine and the API for each medicine were distinct performance obligations.</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 determined our transaction price to be $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_6dbe3e18253b42678289e91bfc07aa2b" contextRef="c20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">108.4</ix:nonFraction>
    million, comprised of the following:</div>
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  </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 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="c20170101to20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">75</ix:nonFraction> million from the upfront payment;</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 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="c20170101to20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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 2017; 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 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:PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" id="Fact_844ad8b58c81489eb92908f6d9b9a1e0" contextRef="c20171231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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>
  <ix:continuation id="Text_7d58284b292a4a309b54f7c4276fc8bf140" continuedAt="Text_7d58284b292a4a309b54f7c4276fc8bf141">
<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 allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:</div>
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  </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 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="c20171231_ProductOrServiceAxis_ResearchAndDevelopmentServicesForPelacarsenMember_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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>
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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;">$<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_051befe7d00048df8a2b3cb0405d5ae3" contextRef="c20171231_ProductOrServiceAxis_ResearchAndDevelopmentServicesForOlezarsenMember_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">40.1</ix:nonFraction> 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>
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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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_b3744373869c4288908b09e14ce88277" contextRef="c20171231_ProductOrServiceAxis_PelacarsenActivePharmaceuticalIngredientMember_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.5</ix:nonFraction></span>
            million for the delivery of pelacarsen API; and</div>
        </td>

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</table>
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  <ix:continuation id="Text_7d58284b292a4a309b54f7c4276fc8bf146" continuedAt="Text_7d58284b292a4a309b54f7c4276fc8bf147">
<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 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="c20171231_ProductOrServiceAxis_OlezarsenActivePharmaceuticalIngredientMember_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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>
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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 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>
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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 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>
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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="c20231231_ProductOrServiceAxis_PelacarsenActivePharmaceuticalIngredientMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of any future royalty payments on pelacarsen. Refer to Note 7, <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 Medicine for the Treatment of Lp(a)-Driven Cardiovascular 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 August 2023, we entered into a collaboration and license agreement with Novartis for the discovery, development and commercialization
    of a novel medicine for patients with Lp(a)-driven cardiovascular disease, or CVD. Novartis is solely responsible for the development, manufacturing and potential commercialization of the next generation Lp(a) therapy.</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;">F-26</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </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_e7f12a6400a4493abc4b2e919f3dec81" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">730</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_c526c9b3aac3498eba1daf4a7d4ed9b9" contextRef="c20231001to20231231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million upfront payment, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_35d21584d311403db335fec885d08698" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">155</ix:nonFraction> million in development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_820c0c4db93943189c8c0d43dce4586e" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">105</ix:nonFraction>
    million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_36bd04df93434800be4f1854ac45250e" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">410</ix:nonFraction> million in sales milestone payments. In addition, we are eligible to receive tiered
    royalties ranging from <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_5b492ad60db14f8a8bf151441f4aa1bf" contextRef="c20230101to20231231_RangeAxis_MinimumMember_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">10</ix:nonFraction> percent to <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_2c6c32bec6f34431ae2264d3cde44dc1" contextRef="c20230101to20231231_RangeAxis_MaximumMember_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent
    on net sales. From inception through December 31, 2023, we have received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_992231ab48fe4d57af8fc641802cc712" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million from the upfront payment we received under this collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_b211469b14f24bd6859fae30e7995afc" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">5</ix:nonFraction> million if we designate a development candidate under this collaboration.</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;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_5b04e66a2f85491eb8b7b3a42796fa13" contextRef="c20230831_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Novartis. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_69d0edf04589477ebfacfa1cea7a2d4c" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million upfront payment we received in the fourth quarter 2023. We allocated the transaction price 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. We currently estimate we will satisfy our performance obligation at the
    end of the research term in June 2024.</div>
</ix:continuation>
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  </div>
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  <ix:continuation id="Text_7d58284b292a4a309b54f7c4276fc8bf162" continuedAt="Text_7d58284b292a4a309b54f7c4276fc8bf163"><ix:nonNumeric name="us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" id="Text_f417927e6ea44049a9024dea0c69d56b" contextRef="c20230101to20231231_TypeOfArrangementAxis_NovartisCollaborationMember" escape="true" continuedAt="Text_0b1171ad47cf43bf94d5c5fefdc2ef581">
<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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Novartis (in thousands, 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>
        </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;">2023</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;">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>

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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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          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Novartis</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>
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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_4ff5f9c394c349349b7bc24fd95d7574" contextRef="c20210101to20211231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,526</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <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;">Percentage of total revenue</div>
        </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:ConcentrationRiskPercentage1" id="Fact_1f40d9d87ee4435c83ab9656d281b655" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">4</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; 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;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; white-space: nowrap;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less than <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_130e18fe0f0c441186a0e17a58f664d9" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" 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; 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:ConcentrationRiskPercentage1" id="Fact_3cbf0264fff04ba19d7c857cee72d9f4" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">3</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our consolidated balance sheet at December 31, 2023 included deferred revenue of $<ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_87d3106b1a1148dea7b789814a61c3f6" contextRef="c20231231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">30.0</ix:nonFraction> million related to our relationship with Novartis. We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_785f8268f75046d48e4290f4853be00e" contextRef="c20221231_TypeOfArrangementAxis_NovartisCollaborationPelacarsenMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction>t have any deferred revenue from our relationship with Novartis at December 31, 2022.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Roche</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 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 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. As a result, Roche is responsible for all global development, regulatory and commercialization activities and costs for tominersen.</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 up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_d8d42ebb32dc46b7895c83156cf73607" contextRef="c20231231_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="c20231231_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="c20231231_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="c20231231_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="c20231231_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="c20231231_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="c20231231_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 collaboration. From inception through December 31, 2023, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_3aa74885781e415aa4fe5dd8e04e1eda" contextRef="c20231231_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="c20231231_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="c20131231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U011" 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="c20131231_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 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 period in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In 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 independent data monitoring committee, or 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 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 multiple studies in <ix:nonFraction name="ions:NumberOfDiseaseIndications" id="Fact_748d8e6ad1bb43a384bba3995dac28ea" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U014" 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_2809887bb083437a90a9b96801dc7ac3" contextRef="c20231231_ProductOrServiceAxis_ImmunoglobulinANephropathyMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U014" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> for the treatment of patients with immunoglobulin A, or IgA, nephropathy, or IgAN, and <ix:nonFraction name="ions:NumberOfDiseaseIndications" id="Fact_33191bc87cff451284262a2fbdef6e22" contextRef="c20231231_ProductOrServiceAxis_GeographicAtrophyMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U014" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> for the treatment of patients with GA, the advanced stage of dry AMD. In April 2023, Roche initiated a Phase 3 study of IONIS-FB-L<sub>Rx</sub> in patients with IgAN.</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 in patients
      with IgAN, </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;">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="c20220101to20221231_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 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="c20231231_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="c20231231_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="c20231231_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="c20231231_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 milestone payments, up to $</span><ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_541e131f3c6b4c92914c6be252062f60" contextRef="c20231231_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 milestone payments and up to $</span><ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_a41faf144bd64eda8d77e690e142dd36" contextRef="c20231231_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="c20230101to20231231_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, 2023,
    we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_c786e47ad0b540fbb376640b5b6b6aba" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">135</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="c20231231_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="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Roche. From inception through December 31, 2023, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_f2a4482e638e473f8466afadc352df31" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">97</ix:nonFraction> million in upfront and milestone payments in
    the transaction price for our R&amp;D services performance obligation under this collaboration, including $<ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_23e8a7ea882b448e860d5d6844b1339a" contextRef="c20220101to20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">22</ix:nonFraction> million of milestone payments we
    achieved in 2022. 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 fourth quarter
    of 2024.</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;">RNA-Targeting Medicines for Alzheimer's Disease and Huntington'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 September 2023, we entered into an agreement with Roche to develop <ix:nonFraction name="ions:NumberOfEarlyStagePrograms" id="Fact_9c3e4ea93aaf4a3bb05b35153d252556" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> undisclosed early-stage programs for RNA-targeting investigational medicines for the treatment of AD and HD. Under the agreement, we are responsible for advancing the <ix:nonFraction name="ions:NumberOfEarlyStagePrograms" id="Fact_2fe613bdfb1c49db987a5988045d8b95" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> programs through preclinical studies and Roche is responsible for clinical development, manufacturing and commercialization of the medicines if they
    receive regulatory approval.</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_7664254b686241a0b11ebc9ea18d163f" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">625</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_bf3f3e668d184752b5747be4d075c0af" contextRef="c20231001to20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million upfront payment, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_aa2e94aa8792409880dcb3db6ed96c21" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">167</ix:nonFraction> million in development milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_c439b36908144ae7b03553338428316e" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">398</ix:nonFraction>
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales. From inception through December 31, 2023, we have received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_1a413e3c07c4442cb7fe10585f566939" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million from the upfront payment we received under this collaboration. We will achieve the next
    payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_c5283e859d7c49818334cf7739246fb6" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.5</ix:nonFraction> million if we advance 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;">We identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_323098af4da04086b03a3676e1b17c62" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> performance
    obligations under this new agreement, comprised of R&amp;D services for each of the <ix:nonFraction name="ions:NumberOfEarlyStagePrograms" id="Fact_4910e794f96649e2841a4bcb84ac292b" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> separate programs. We determined the transaction price
    to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_9b42b643057148369520d4bc807f7d5d" contextRef="c20231231_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million upfront payment we received in the fourth quarter 2023. We allocated the transaction price based on the estimated
    stand-alone selling price of each performance obligation as follows:</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;">$<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_dbb92ada6f884b8a95d253549dccc2dc" contextRef="c20231231_ProductOrServiceAxis_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">45</ix:nonFraction> million for the R&amp;D services for the investigational
            medicine for AD; 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</span><ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_a47e2a76c57e4695b2daade551ea224c" contextRef="c20231231_ProductOrServiceAxis_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_TypeOfArrangementAxis_RocheCollaborationRNATargetedProgramsForADAndHDMember" 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 for the R&amp;D services for t</span>he investigational medicine for HD.</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 recognizing revenue for our R&amp;D services performance obligations as we perform services based on our effort to satisfy our
    performance obligations relative to our total effort expected to satisfy our performance obligations. We currently estimate we will satisfy our performance obligations at the end of the research terms of March 2024 and March 2025 for the
    investigational medicines for AD and HD, respectively.</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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Roche (in thousands, 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;">2023</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;">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>

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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;">Revenue from our relationship with Roche</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; 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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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_43d5265cf6164fce9ca88f18b5897dc3" contextRef="c20220101to20221231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">67,202</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>
        </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_20872827ad6c4817bcf759078e23498f" contextRef="c20210101to20211231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,241</ix:nonFraction></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>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">6</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_cf5ca05dc07c4448bdda2353f8ed8769" 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_6490dfcad60e494083f50ae6646f73e4" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember" 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%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-28</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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 </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2022<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="c20231231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">36.7</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="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 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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Otsuka</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 2023, we entered into an agreement with Otsuka Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe.
    We are responsible for the ongoing development of donidalorsen. We retained the rights to commercialize donidalorsen in the U.S. and in the rest of the world assuming regulatory approval.</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_83e4f69e2fa64d648c05bebd72b158cb" contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">185</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_8a8d9e182b6846d8aa9b4ac6ec87b7b0" contextRef="c20231001to20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction> million upfront payment, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_1475c224f3c9433097c24ab20e813634" contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">50</ix:nonFraction> million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_4964ef3fe3244ce3a91629a9af0e6fac" contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">70</ix:nonFraction>
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties ranging from <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_d53ff3dfc7e5444fb6b236e2bece9a73" contextRef="c20230101to20231231_RangeAxis_MinimumMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent to <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_d5b20d1cba704a8cb0fffbe29fba3f2b" contextRef="c20230101to20231231_RangeAxis_MaximumMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">30</ix:nonFraction> percent on net sales. From inception through December 31, 2023, we have received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_8bacb479b10f4a519b6f9f0b60fdf84f" contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction> million from the upfront payment we received under this collaboration. We will achieve the next
    payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_c1d2152e2c604418a9c3c7376ad14171" contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction> million if the EMA accepts a MAA filing for donidalorsen in the EU 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;">We identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_27fb7f4e535a470eaab5dc07fee5038a" contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> performance
    obligations under this new agreement, comprised of our license of donidalorsen to Otsuka and R&amp;D services for donidalorsen. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_ebadc349803b440ebdc2ca77c18844a0" contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction> million upfront payment we received in the fourth quarter 2023. We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:</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;">$<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_bc5e5327115f4deea2ae75dc63832c93" contextRef="c20231231_ProductOrServiceAxis_LicenseOfDonidalorsenMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">56</ix:nonFraction> million for the license of donidalorsen; 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;">$<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_78ea72b1d4a54c649943487acf03c123" contextRef="c20231231_ProductOrServiceAxis_ResearchAndDevelopmentServicesForDonidalorsenMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">9</ix:nonFraction> million for the R&amp;D services for donidalorsen.</div>
        </td>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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 obligations in March 2026.</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 year ended December 31, 2023, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amount):</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>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</div>
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        </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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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</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 </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2023<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_ab2db9a4c2814c19ba0f374053b31f7e" contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
      million related to our relationship with Otsuka.</span></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="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 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="c20230101to20231231_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 and September 2023, we started receiving
    royalties from PTC for TEGSEDI and WAYLIVRA sales, respectively<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-style: italic;">Swedish Orphan Biovitrum AB (Sobi)</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 2021, we began commercializing TEGSEDI and WAYLIVRA in
      Europe and TEGSEDI in North America through distribution agreements with Sobi. </span>Under our distribution agreements, Sobi is responsible for commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. We are
    responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. Under our agreements with Sobi, Sobi does not generally have a right of return. We recognize as revenue the price Sobi
    pays us for the inventory when we deliver the finished goods inventory to Sobi. In addition, we earn a distribution fee on net sales from Sobi for each medicine.</div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-29</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </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 2023, our distribution agreement for TEGSEDI in North America was terminated. As a result, we are currently transitioning
    responsibilities from Sobi to us in order to continue serving the impacted patient community. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In February 2024, we began the process to withdraw the TEGSEDI NDA.</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, 2023, 2022 and 2021, we earned the following revenue from our distribution agreement with Sobi for TEGSEDI in North America (in thousands, except percentage amounts):</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">


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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>

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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;">2023</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;">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: 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;">TEGSEDI revenue from our distribution agreement with Sobi in North America</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>

    <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>

    <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>

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    <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;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; white-space: nowrap;" 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">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; 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;" 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:ConcentrationRiskPercentage1" id="Fact_08f84879a787490da4709449a75caa18" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_SwedishOrphanBiovitrumABDistributionAgreementMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; 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: 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 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 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 2021, we paid $<ix:nonFraction name="ions:PaymentsMadeUnderCollaborationAgreement" id="Fact_5f30af4db40c410198d4adf0cf56a2ac" contextRef="c20210101to20211231_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="c20230101to20231231_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.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Metagenomi</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 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="c20221231_TypeOfArrangementAxis_MetagenomiLicenseAgreementMember" unitRef="U015" 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="c20221231_TypeOfArrangementAxis_MetagenomiLicenseAgreementMember" unitRef="U015" 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:PaymentToLicenseTechnology" id="Fact_537c87b66c264e69b2abf8afc8e75f50" contextRef="c20220101to20221231_TypeOfArrangementAxis_MetagenomiLicenseAgreementMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">80</ix:nonFraction> million to license Metagenomi&#8217;s technologies and will pay Metagenomi certain fees for the selection of genetic targets. We recorded the $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost" id="Fact_e055474b91a641ecbda62b2a56a15444" contextRef="c20220101to20221231_TypeOfArrangementAxis_MetagenomiLicenseAgreementMember" 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. In addition, we will pay
    Metagenomi milestone payments and royalties that are contingent on the achievement of certain development, regulatory and sales events. We will also 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="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 <ix:nonFraction name="ions:NumberOfTherapeuticPrograms" id="Fact_b59f89497d794a21b1c2df7b377e99c3" contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</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="U015" 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="U015" 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="U015" 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="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-30</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Alnylam (in thousands, except percentage amounts):</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>

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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>

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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;">2023</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;">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>

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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: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Alnylam</div>
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    <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>

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        </td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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        </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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          <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>

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    <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_2cfe3b7062dc4a9cb5ee360d01476480" contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">4</ix:nonFraction></div>
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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%;" 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="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">4</ix:nonFraction></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; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</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 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="c20221231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_12c9599416c543e7890f0ee3f45418ed" contextRef="c20231231_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, 2023 and 2022.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5. Investments</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, 2023:</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a3" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a4"><ix:continuation id="Text_2e887f2f82084b1e9b52ea2b0b07d98c1" continuedAt="Text_2e887f2f82084b1e9b52ea2b0b07d98c2">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a4" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a5"><ix:continuation id="Text_2e887f2f82084b1e9b52ea2b0b07d98c2">
<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="c20230101to20231231" 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="c20231231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">68</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="c20230101to20231231" 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="c20230101to20231231" 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="c20231231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">24</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="c20230101to20231231" 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" id="Fact_d60e9c8e586b428c886b9d9653ac0f6e" contextRef="c20231231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">8</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); 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: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" id="Fact_298fc5ad20a2442399af2cd8e8215ece" contextRef="c20231231" 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%; background-color: rgb(255, 255, 255); border-bottom: 4px double rgb(0, 0, 0); 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>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a5" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a6">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a6" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a7">
<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, 2023,
    <ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="Fact_971b070bcf6846b8970847cdbaef1457" contextRef="c20231231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">92</ix:nonFraction> percent of our available-for-sale securities had a maturity of less than <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_e4aa3be8fcd040d0bcd0def824af337d" contextRef="c20230101to20231231" format="ixt-sec:durwordsen">two years</ix:nonNumeric>.</div>
</ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a7" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a8">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a8" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a9">
<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>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a9" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a10">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a10" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a11">
<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 invest in debt securities with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp;
    Poor&#8217;s, Moody&#8217;s or Fitch, respectively.</div>
</ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a11" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a12">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a12" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a13">
<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, 2023, we had an ownership interest of less than 20 percent </span>in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_c487d989afb240aaae9be0536d4b8656" contextRef="c20231231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">seven</ix:nonFraction>
    private companies and <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_cc8fa179d30548a7b52fcdc75fe7eeee" contextRef="c20231231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> public companies with which we conduct business<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
</ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a13" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a14">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a14" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a15"><ix:nonNumeric name="us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock" id="Text_8334d44cad3443a9ab4f38e658200dff" contextRef="c20230101to20231231" escape="true" continuedAt="Text_13a69f73709f4415a8b4726390c896811">
<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>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a15" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a16"><ix:continuation id="Text_13a69f73709f4415a8b4726390c896811" continuedAt="Text_13a69f73709f4415a8b4726390c896812">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a16" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a17"><ix:continuation id="Text_13a69f73709f4415a8b4726390c896812" continuedAt="Text_13a69f73709f4415a8b4726390c896813">
<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>
        </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="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, 2023</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="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">559,967</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#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="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">157</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="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,625</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="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">557,499</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>
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    <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="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">224,711</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="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" 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: #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="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">611</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
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        </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="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">224,164</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="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">513,784</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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">152</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="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,889</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="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">512,047</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_f17e37bd45aa4fdbae4827a34aa7dac9" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,757</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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_8da02b683fe94c99ae3334fe0583bcbf" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">42</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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_f5548b5e22d64358b14bff13c4cde745" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">113</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:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_5215ece6e8674be582ac13fad8e0e02f" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,686</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; margin-left: 18pt; 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: #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_06b37f3d76b24645b428aed40ef7519d" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,316,219</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>

    <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_868aecd154b3411fad39ee7f067ae085" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">415</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_27ce74de3a8d48ed86f8ce84429f7f33" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,238</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_7cbbbf68a23c4d05acea3eb703650eb7" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,311,396</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_68c90e44ae7142faa5c935422fe6ca01" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">243,151</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_0ecb6c8cead3473f9be6b9fc2b15d79f" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,270</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_4f2e99491c92483882c5013894e5a3b4" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">692</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_8078467ba1d947589f274b1470ccc8c7" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">243,729</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_e4c79d28e0dd438c896e0c5148cdbae0" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">110,138</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_c3fb53b35b5e4f0a801fb17377bbe452" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">547</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_f20247b6d2f84ccbbb1dbab68b9cd3d6" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">21</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:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_a656c02b450b4ae39000dbd1d10a2d67" contextRef="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">110,664</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_160b2612c5ff403daa0b23ecdd2866db" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">294,873</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_b1272ac8ac42497ba65853e630ea020a" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,239</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_803581e2009f4b95bf2af6ab10413c74" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">480</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_32fdcfaa188c4467a9bc336b98ee4765" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">295,632</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;">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: #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_4ae16ba11af3451383afc794f381425b" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,466</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_fee237831c094d6db8d66deaea062f6b" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7</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_b46d7b7d41284f92910e48dd0d37da98" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4</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_072a76897a5042d8befaddf252441541" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,469</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; margin-left: 18pt; 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: #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_b71803caad4d4886ad41f6bbc5e209f5" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">651,628</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_8a0a49d9cc1e4c129249d0be27e415f2" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,063</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_0ca92b9c73b2492aadcfbe4f82a50cb4" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,197</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_91167061047b48f4b8610c1a21447584" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">653,494</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: 27pt; 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: #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">
          <div style="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;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_a5e37551797746d7832fc5653898ad64" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,967,847</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">
          <div style="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;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_5784263002924b25aff1cb14f626bf7f" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,478</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">
          <div style="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;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_7654b51ce0a5448fa1c5723b77e4a3cd" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,435</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">
          <div style="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;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_fb3ebfc0325446129501360d15bf62ff" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,964,890</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;">Equity 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">&#160;</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">&#160;</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">&#160;</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">&#160;</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;">Publicly traded equity securities included in other current assets (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">
          <div style="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:EquitySecuritiesFvNiCost" id="Fact_cef09f69ddec4b3dabee2b4ce3e2377b" contextRef="c20231231_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: #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:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_3f654be6d96e41e4b4713c77ccf1c8e3" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">236</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:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_3d2a388042994347ab5102d669861a7d" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,832</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:EquitySecuritiesFvNi" id="Fact_2d87969d9ae34d49b910e43cebb1d676" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,301</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;">Privately held securities included in deposits and other assets (3)</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:EquitySecuritiesFvNiCost" id="Fact_9ebd36323e384809b15acae0a3551932" contextRef="c20231231_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: #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:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_aed73c2c4de9479b940ffa549e9fedd0" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,001</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:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_1f1394dc79044e9197f515e0b7bca042" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,125</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:EquitySecuritiesFvNi" id="Fact_acab1218ec2e41199e1b320128741143" contextRef="c20231231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" 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: #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; margin-left: 18pt; 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: #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">
          <div style="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;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_1f62fdc7a62342f68a33d50b3bde0a58" contextRef="c20231231" 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: #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">
          <div style="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;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_c2b1f14b00d941b6b317ee97742c8d96" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,237</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">
          <div style="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;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_9d1928afc7224324b66d25fddff38253" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,957</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">
          <div style="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;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_594521b1bd6241bea5eaec95f58271c0" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,292</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; background-color: #FFFFFF;">
          <div style="text-align: left; margin-left: 36pt; 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: #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">
          <div style="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: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_afee4ce7ef954363a1010e810f1ae960" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,002,859</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">&#160;</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">
          <div style="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: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_a346c4f456874316909407a757ecc1b7" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,715</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">&#160;</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">
          <div style="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: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_0bd6c064edff43c09905fc28e289473e" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,392</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>

    <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">
          <div style="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: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_f35d561e61484f2295cadeeb2d03bdbd" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,014,182</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">&#160;</td>

  </tr>


</table>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>
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<div><br/>
  </div>
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  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a18" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a19"><ix:continuation id="Text_13a69f73709f4415a8b4726390c896814" continuedAt="Text_13a69f73709f4415a8b4726390c896815">
<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>
        </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="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_8ea119980dc64034994a6b7ad86f848c" 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_6df2fbe2752e4bd0bb77abf8abe0ae29" 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_73421ff544c5487b9e733e95b060b569" 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_c85091a5a55a45a881f09b4c8c70a29c" 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_da1b311c89004135b55ecee7befa549d" 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_6c6ca7c3257b46848b5da442e9d2b424" 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_f8696120bd5749f081186004728dcfec" 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_ba83c8acf52443779871f0f7f21e0f69" 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_267f46317f0b40caa2f037611c038a1e" 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_2d25c6a792494377addd272a5b8dded6" 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_f56cc4d0d90d4e7fbb8f72585969858c" 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_0c7a5d61dae34de8a30b14b8802b8785" 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_2665cd241db44217ad8643b9ae2a63da" 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_5244a18f7849464e8277366dd5790037" 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_703babc31466440681b56330914ed672" 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_8732df0d6eac436fa8da11aab067289a" 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_7b97de9bcc984df7af60b39c75fdeb48" 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_88e5441a81b14f4288f761f8a4a76ff3" 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_47e5b79f22674ebbaa3309d689033388" 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_9cd1a441eb6d42e4b43b562c28b4a6ea" 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; margin-left: 18pt; 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_f91f4bf7895e4255b6fb1606547e04c4" 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>

    <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">
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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">
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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_c8341442a25e450b8c2a53f28afa5bbb" 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_627bd1dd191a4e2aa0ffcac3c093515e" 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_de7b01c6aeff4c67be7342b578227fe7" 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_6dd609ef5c9d4c5abd47201f2f3c3971" 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_01ade62c43ae4d1d9d121b813ab06110" 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_1a4e37f7b16f498caa99b193ac3977d1" 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_9e774f36b3824b5da1f596ef542f70e8" 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_fcf3826f90e44039b289f8286697222d" 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_3834f60c806146fdb57604df4ca44d5f" 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_3b50fc36268c472c83543a498f74c6a3" 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_3cc6fe9c6c684eabbb359b5b57a83381" 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_f9f79be238454b459039ee2cf29f6635" 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_285a93f311de42a8b8b01192c7d0cee6" 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; margin-left: 18pt; 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="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_80c5acbabb8c4f0bb30f07636779a6ef" 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_2d2b1cb797c643148d37d334e933eeb2" 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_2bbc29a667a94cb99ff6c9f040ebeea6" 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; margin-left: 36pt; 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="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_609132a66d2f4130b140a88c2fb0c89d" 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_b09e4761e6054b25a622ed40b8db284e" 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_4de7d9b3be6d447db4b3c3fe0b8f036b" 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; 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;">Publicly traded 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="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_88ed4a2745c54e14a622755a003ef7d5" 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_b4cdd38512ef47d9b5d3df0de25143e1" 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_c71d4b805e374b9696b1907d0c3b8708" 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;">Privately held 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="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_f166a5e138d3457b82d04bfee0b2aaa8" 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_377148fd543d4bcd9b069e1883f63342" 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_250e88ec455a48818d6c542e743f1801" 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; margin-left: 18pt; 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="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_c7bf32577ac44c999892ccbf176d194e" 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_7050ac2adf394b31b986c11c8b0618f6" 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_b3f9adef6e924b3c91c0bc0573208fed" 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; margin-left: 36pt; 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">
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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%; 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="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,451</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="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,997</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="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,772,302</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_825bdc08a3aa469db0ec9c1ecad9b82a19" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a20"><ix:continuation id="Text_13a69f73709f4415a8b4726390c896815" continuedAt="Text_13a69f73709f4415a8b4726390c896816">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_825bdc08a3aa469db0ec9c1ecad9b82a20" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a21"><ix:continuation id="Text_13a69f73709f4415a8b4726390c896816" continuedAt="Text_13a69f73709f4415a8b4726390c896817">
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  <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_825bdc08a3aa469db0ec9c1ecad9b82a21" continuedAt="Text_825bdc08a3aa469db0ec9c1ecad9b82a22"><ix:continuation id="Text_13a69f73709f4415a8b4726390c896817" continuedAt="Text_13a69f73709f4415a8b4726390c896818">
<div><br/>
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</ix:continuation></ix:continuation>
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  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

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        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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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;">(3)</td>

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  </tr>


</table>
</ix:continuation></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;"><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, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;(in thousands, except for number of investments):</span></div>
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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; white-space: nowrap;" 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>
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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; white-space: nowrap;" 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>
        </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>

    <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="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U016" decimals="0" scale="0" format="ixt:num-dot-decimal">297</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="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">323,708</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="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">553</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="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">178,183</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="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,764</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>

    <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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_8fb2ae4a1ec045fa9a3e85eb73fd7579" contextRef="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">501,891</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; 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="c20231231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,317</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>

  </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="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U016" decimals="0" scale="0" format="ixt:num-dot-decimal">63</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%; 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="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">199,372</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="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">246</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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        </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="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,777</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="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">386</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="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">214,149</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="c20231231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">632</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>

  <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="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U016" decimals="0" scale="0" format="ixt:num-dot-decimal">34</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="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">325,966</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="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,031</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="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">131,000</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_15db03a6433941238fd306654da22142" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,338</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:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_9c658483c775407ba8d359cb397e54eb" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">456,966</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:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_c185480eb0914a3295c76692e3bcadd1" contextRef="c20231231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,369</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%; padding-bottom: 2px;">
          <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; 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_71c2fda61dc846298eeff9b0ca38115c" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U016" decimals="0" scale="0" format="ixt:num-dot-decimal">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>

    <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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_6990d89425474cfc9c4b8bf0d8cf7439" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,352</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; 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_4a48d7c90c5a4a0bbe2ae5be47316023" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17</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; 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_a28ea3274df5428e98f07b9d17b49fab" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,888</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; 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_687e88a52c8446078d869df0c183470d" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">100</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; 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:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_c17115e0327d4b7ca7c6e3aadbaaf14f" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,240</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; 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:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_8c469d84d7df46f7a259af6e5d56319a" contextRef="c20231231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">117</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: 16%; padding-bottom: 4px; 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;">Total temporarily impaired securities</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%; border-bottom: #000000 double 4px; 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 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_c5a13e110d15472bb7209a893f75760c" contextRef="c20231231" unitRef="U016" decimals="0" scale="0" format="ixt:num-dot-decimal">455</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; 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_bcffdf58f44a4915b5c47f23299cb0a4" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">857,398</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; 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_258d034cad9c41d5818f3ff1c5e9ac54" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,847</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; 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_8d829588e22141b8a62fed91d7622b5e" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">331,848</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; 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_36b440f266f44cfa9a6ffb88f94ffc3f" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,588</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; 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:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_29ce681916874294a263914fba442f04" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,189,246</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; 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:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_c6330165fcf44008a4bcbadea16125b1" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,435</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>
</ix:continuation></ix:continuation>
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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 believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates
    since purchase rather than underlying credit deterioration for any of the issuers. We believe it is more likely than not that we will be able to hold our debt securities with declines in value to maturity. Therefore, we intend to hold these securities
    to maturity and anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</div>
</ix:continuation></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;">F-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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:FairValueDisclosuresTextBlock" id="Text_a080c2e549ed48798336fbfa516a174a" contextRef="c20230101to20231231" escape="true" continuedAt="Text_9d4cdf954cf14547994f684656665f1d1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6. Fair Value Measurements</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;">The following tables present the major security types we held at December 31, 2023 and 2022&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. 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>
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  </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; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" 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, 2023</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; white-space: nowrap;" 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; white-space: nowrap;" 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="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">185,424</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">
          <div style="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="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">185,424</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">
          <div style="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="c20231231_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 (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_bd40b54476544609af8d4027bb17852a" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">801,228</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="c20231231_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">
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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: 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 (3)</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="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">334,828</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="c20231231_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="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">334,828</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 (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_f597ef484dc849b3869c0b24b7e47ca0" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">807,679</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="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">807,679</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="c20231231_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 (3)</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="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">21,155</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="c20231231_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="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">21,155</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>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (5)</div>
          </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:EquitySecuritiesFvNi" id="Fact_3a7b94ae1575483d99cdff167336737c" contextRef="c20231231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,301</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:EquitySecuritiesFvNi" id="Fact_dcbce3ea27dc430f9082c8d96ba2c86b" contextRef="c20231231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,301</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:EquitySecuritiesFvNi" id="Fact_9b2894878d734371a537f270d1142205" contextRef="c20231231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_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%; 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: -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; 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:AssetsFairValueDisclosure" id="Fact_41aa8ca715a246c6ab132f68d33110c2" contextRef="c20231231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,156,615</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:AssetsFairValueDisclosure" id="Fact_14262b51a03546e9864249ccb9ca4a20" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">999,404</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:AssetsFairValueDisclosure" id="Fact_8134fdf4a60f4810b009f807fc4ce04e" contextRef="c20231231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,157,211</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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</ix:continuation></ix:continuation>
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<div><br/>
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_9d4cdf954cf14547994f684656665f1d6" continuedAt="Text_9d4cdf954cf14547994f684656665f1d7"><ix:continuation id="Text_3487f45eb5234626b46b261761c59c824" continuedAt="Text_3487f45eb5234626b46b261761c59c825">
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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; white-space: nowrap;" 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; white-space: nowrap;" 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; white-space: nowrap;" 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_6f9a8b7bb0274b6aa4ebdbfd8ec1cda4" 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_d022e13f5bfc44a485ff5fc107b87349" 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_0dd4548c72224cd6975d2b0c28babec7" 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 (4)</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="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_fb9b7215206045289d5ac989482b34ac" 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_9e1bc60cb2a5438ba5a8181266e5e834" 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 (3)</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="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_f00f0183fbdb414bb8ace8c09326de91" 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_6bff7c97ac774c11923e8315e813ef18" 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 (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_3f43d316784545c8b69beec4e9b1bf54" 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_9f168d9ee16e4f3b813f38c507fa28b1" 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_0e067bc23c4d4301839ded59e2581b10" 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 (3)</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="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_7ea5abb7b7dc46d8b9f0f873e9607020" 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_e8c040876cb94663b41bc3252cdfe50f" 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 (3)</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="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_ba6ea93809db4df2be5272d7fb3a6008" 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_c660da70931c462ba2056be05730a5c3" 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 (5)</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="c20221231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_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%; 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="c20221231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_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%; 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="c20221231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_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%; 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_57c8091a5a114c3c8f6bccd694eb8b0e" 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_9efce47d082648b086daa33248918cfb" 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_45cbd4a07e9d4ab8b914ee2d30888ee9" 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>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_9d4cdf954cf14547994f684656665f1d7" continuedAt="Text_9d4cdf954cf14547994f684656665f1d8"><ix:continuation id="Text_3487f45eb5234626b46b261761c59c825" continuedAt="Text_3487f45eb5234626b46b261761c59c826">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_9d4cdf954cf14547994f684656665f1d8" continuedAt="Text_9d4cdf954cf14547994f684656665f1d9"><ix:continuation id="Text_3487f45eb5234626b46b261761c59c826" continuedAt="Text_3487f45eb5234626b46b261761c59c827">
<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_9d4cdf954cf14547994f684656665f1d9" continuedAt="Text_9d4cdf954cf14547994f684656665f1d10"><ix:continuation id="Text_3487f45eb5234626b46b261761c59c827" continuedAt="Text_3487f45eb5234626b46b261761c59c828">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_9d4cdf954cf14547994f684656665f1d10" continuedAt="Text_9d4cdf954cf14547994f684656665f1d11"><ix:continuation id="Text_3487f45eb5234626b46b261761c59c828" continuedAt="Text_3487f45eb5234626b46b261761c59c829">
<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_5618a89e2fcf4ea18d4496f6d55029f1" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_881350eb47ef4105abdf8d5461f21f45" contextRef="c20231231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">33.0</ix:nonFraction> million was included in cash and cash equivalents, 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_9d4cdf954cf14547994f684656665f1d11" continuedAt="Text_9d4cdf954cf14547994f684656665f1d12"><ix:continuation id="Text_3487f45eb5234626b46b261761c59c829" continuedAt="Text_3487f45eb5234626b46b261761c59c8210">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_9d4cdf954cf14547994f684656665f1d12" continuedAt="Text_9d4cdf954cf14547994f684656665f1d13"><ix:continuation id="Text_3487f45eb5234626b46b261761c59c8210" continuedAt="Text_3487f45eb5234626b46b261761c59c8211">
<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_77eb85d4142a44a68a7c6b25a7169d1c" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in short-term investments in our consolidated balance sheets.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_9d4cdf954cf14547994f684656665f1d13" continuedAt="Text_9d4cdf954cf14547994f684656665f1d14"><ix:continuation id="Text_3487f45eb5234626b46b261761c59c8211" continuedAt="Text_3487f45eb5234626b46b261761c59c8212">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_9d4cdf954cf14547994f684656665f1d14" continuedAt="Text_9d4cdf954cf14547994f684656665f1d15"><ix:continuation id="Text_3487f45eb5234626b46b261761c59c8212" continuedAt="Text_3487f45eb5234626b46b261761c59c8213">
<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_cc6012bb3041434399bdb287399a913a" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_99b5e575cc9b4c04a4aebda207f82f5d" contextRef="c20221231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">11.0</ix:nonFraction> million was included in cash and cash equivalents, 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_9d4cdf954cf14547994f684656665f1d15" continuedAt="Text_9d4cdf954cf14547994f684656665f1d16"><ix:continuation id="Text_3487f45eb5234626b46b261761c59c8213" continuedAt="Text_3487f45eb5234626b46b261761c59c8214">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_9d4cdf954cf14547994f684656665f1d16" continuedAt="Text_9d4cdf954cf14547994f684656665f1d17"><ix:continuation id="Text_3487f45eb5234626b46b261761c59c8214">
<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_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_9d4cdf954cf14547994f684656665f1d17" continuedAt="Text_9d4cdf954cf14547994f684656665f1d18">
<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; font-style: italic;">Convertible Notes</div>
</ix:continuation>
  <ix:continuation id="Text_9d4cdf954cf14547994f684656665f1d19" continuedAt="Text_9d4cdf954cf14547994f684656665f1d20">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_9d4cdf954cf14547994f684656665f1d20">
<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_fec8350d2b584c31a556d0714630ce22" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes, <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_47cf6f98169049fbac9d864c715e8edb" contextRef="c20231231_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_bd322b8313e14411b434a697d8be9cf3" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes had a fair value of $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_f659cb73d02d4ef08f0df32bb027b149" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">661.1</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_f0e3f2364810404e841460fd9d182b2b" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">667.8</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_4dd54a5e498144848bb917146895383f" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">42.4</ix:nonFraction> million at December 31, 2023,
    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 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;">F-33</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:DebtDisclosureTextBlock" id="Text_1f7799e29d9c4fd5ac2c30d64ad9a625" contextRef="c20230101to20231231" escape="true" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec71">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Long-Term Obligations and Commitments</div>
</ix:nonNumeric>

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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec72" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec73"><ix:nonNumeric name="us-gaap:ScheduleOfDebtInstrumentsTextBlock" id="Text_a4959bdb175f4cf6a490ada2282e4021" contextRef="c20230101to20231231" escape="true" continuedAt="Text_70f08be58b3249bd8d59246962933d431">
<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_1e6cd6cf7156470da11a49cfddf68ec73" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec74"><ix:continuation id="Text_70f08be58b3249bd8d59246962933d431" continuedAt="Text_70f08be58b3249bd8d59246962933d432">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec74" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec75"><ix:continuation id="Text_70f08be58b3249bd8d59246962933d432">
<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;">2023</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;">2022</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: 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_9be7f56fb8e842d797590e6fa844bd8a" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_0cf43b8e8e7c41779083e1aafe9c5b6d" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction></ix:nonFraction></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_9d8ce4d747b14e70b17d777d1cc23dd4" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">562,285</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:ConvertibleDebt" id="Fact_76e0c4ca0c534ca589e77e4c976b992c" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" 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: 76%;">
          <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="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4ee7f30dae904ac9b29e30d4ae582e81" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction></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="us-gaap:ConvertibleDebt" id="Fact_cc24fb43c0744f1c98325749d3d1c0eb" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">625,380</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;">
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            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">
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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%;">
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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>

  </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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">178,969</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:OperatingLeaseLiability" id="Fact_8f7e7fa2aaf644beafdec103f6046e51" 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>

  </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="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,998</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">33,714</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="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>

  </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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,922,943</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="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>

  </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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,831</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="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>

  </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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,914,112</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="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>

  </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>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec76" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec77">
<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, 2023, our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5d3c0e0284834ea7a2bba01a0abcae7a" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%
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</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec77" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec78">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec78" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec79">
<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_1e6cd6cf7156470da11a49cfddf68ec79" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec710">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec710" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec711">
<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_2be25c7a5c72472e9c15210dd1e5d28a" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>%
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</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec711" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec712">
<div><br/>
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</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec712" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec713">
<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 2023, we completed a $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_2827f988857f4d83a88b2709d9e03496" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">575.0</ix:nonFraction>
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</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec713" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec714">
<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;">At December 31, 2023, we had the following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b863244551354c4ba0f150236fa87941" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>%
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</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec715" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec716"><ix:continuation id="Text_e7d1e889d4ff4b3d834a68ac23705b8f1" continuedAt="Text_e7d1e889d4ff4b3d834a68ac23705b8f2">
<div><br/>
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec716" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec717"><ix:continuation id="Text_e7d1e889d4ff4b3d834a68ac23705b8f2">
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  <tr>

    <td valign="bottom" style="vertical-align: top; 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: top; border-bottom: #000000 solid 2px;" colspan="2">
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        </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">
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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: 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">
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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: 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_6bfb094eab7041389566a848570cbbe5">June 2028</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; width: 88%;">
          <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; 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:DebtInstrumentInterestRateStatedPercentage" id="Fact_e1d091b2df1d47028e7c17396441fb80" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</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: top; width: 88%; 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; 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:DebtInstrumentInterestRateEffectivePercentage" id="Fact_0dc0b20f31a942798c3ab1359dd806a2" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">2.3</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: 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_f56a3eac5087438ea4564f05d5033780" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">53.73</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;">Total shares of common stock subject to conversion</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:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_09bd02bea9714ddbb22f039a7b396d9f" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.7</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>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec717" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec718">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec718" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec719">
<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_f5b5a23692f0422d8037c5dd1c16fade" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%
    Convertible Senior Notes and Call Spread</div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec719" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec720">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec720" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec721">
<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 completed a $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_e356cca79255453a9744770e7aab33b4" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">632.5</ix:nonFraction>
    million offering of convertible senior notes. We used $<ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_4de3897ac3004dd1afac4be2c42bf1f7" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">319.0</ix:nonFraction> million of the net proceeds from the issuance of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ae7002548a534fee872a8e938e39b15c" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes to pay the remaining $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_ca75ade69e7442869526532bd706b3dd" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">309.9</ix:nonFraction> million
    principal balance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9c88b33e6c8542d4a643427942f4e71b" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes in 2021.</div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec721" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec722">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec722" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec723"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_599676c995b8459d807f45a7ee7d2f44" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" escape="true" continuedAt="Text_861b78249d3f44eda002cff586e008fa1">
<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, 2023, we had the following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_cf6dcedc94a145b888849ad4a5c7cdb5" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes outstanding (in millions, except interest rate and price per share data):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec723" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec724"><ix:continuation id="Text_861b78249d3f44eda002cff586e008fa1" continuedAt="Text_861b78249d3f44eda002cff586e008fa2">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec724" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec725"><ix:continuation id="Text_861b78249d3f44eda002cff586e008fa2">
<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;"> </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_6d46b8c9d8784f0fa3a450459c902acb" contextRef="c20231231_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_e8faed5233594fb6bf822eaf5dce7321" contextRef="c20231231_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_350bc75ec4184041835a9e5d0abbe608" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.2</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: 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_77100aa329424b42b6f03dc4fa1e2472">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; width: 88%;">
          <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; 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:DebtInstrumentInterestRateStatedPercentage" id="Fact_6d45cad18839462fa92cba3b7325e8b0" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</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: top; width: 88%; 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; 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:DebtInstrumentInterestRateEffectivePercentage" id="Fact_260bb8f54ea846abb3af6de44c421a97" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </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_4d4305ef91884023b859a267d99ab638" contextRef="c20231231_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_0e8e01a4405d49f9b71f725ea3741819" contextRef="c20231231_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_9b29e5e197724eaeaa88134c9db47e86" contextRef="c20231231_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>


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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-34</div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></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 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_b22585535cfb466eb1e1615019206acb" contextRef="c20231231_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_ab040372e7e74fc3812280d6edee6f21" contextRef="c20231231_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_598593809d9544798fe271f12c9023fb" contextRef="c20231231_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_cbb00c2783694753bef550b9864ee799" contextRef="c20231231_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_129e260b2ff84c1db67e2212a1785983" contextRef="c20210101to20211231_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_25825ced735845a59993eed7890d4b22" contextRef="c20210101to20211231_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_4f7a63f450c14b14afc04dd8bf6effa3" contextRef="c20210101to20211231_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_f0c3c1424f334a3dada4d019d37f7a67" contextRef="c20231231_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_a887ff3cb730420a8161a0af503a358d" contextRef="c20231231_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_775c5689ca3941d9913a9c6a75bd4518" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%
    Notes, or <span style="-sec-ix-hidden:Fact_c2c8af8268614a7d9201a587fc5822f5">April 2026</span>. The note hedges and warrants are separate transactions and are not part of the terms of our&#160; <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ad5009d3de5c4135aa6fc1d1e09990ca" contextRef="c20231231_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_c92efdfde6094e73bb58539e70cac496" contextRef="c20231231_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>
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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 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: 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_a1630fc496cc4b6b8fca442ebcbb1f31" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%
    Convertible Senior Notes and 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 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of
    our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_741bd24af8454bb8b57e1238ce0f360e" contextRef="c20231231_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_8fe4c3bf98884e558d3617a5c9500acd" 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_f20ee7aa37e84ac2997fe3950fccd36c" contextRef="c20231231_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_34f127b663394d64a09c8f28308a2191" 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_a52eda79373d4bb1be58b66bff61219b" contextRef="c20231231_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_38bf866f0d0640faa683c6433495028f" 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_06096a47ac82472ba19a888fcbdb199f" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes.</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 2023, we repurchased $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_4ce45938c9ac49109b6af8dd34990118" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">504.4</ix:nonFraction>
    million of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_303242a9804e4932bd78783ac53b820a" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes. We are holding the repurchased <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a624f90bf6a34fda82a36db2fc1de814" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes in treasury until maturity. As a result, the remaining principal balance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8a455c1ec05043ab82a4e880d971ee36" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%
    Notes was $<ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_f6079dd81feb4198b58a4aec32d79088" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">44.5</ix:nonFraction> million as of December 31, 2023.
    Additionally, during the year ended December 31, 2023, we recorded a $<ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_9b9f41e3cd3b4da69cb768223bcf23ab" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_IncomeStatementLocationAxis_OtherNonoperatingIncomeExpenseMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">13.4</ix:nonFraction> million gain on the early retirement of debt, which we recorded as other income in our consolidated statements of operations. The gain on the early retirement of our debt is the difference
    between the amounts paid to repurchase our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_26627e77fb794a31a38c5064d6a5a1a6" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes and the net carrying balance of the liability at the time that we completed the
    repurchases.</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;">At December 31, 2023, we had the following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f722285a927a43d89e710b4017140ca7" contextRef="c20231231_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>
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  <tr>

    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;"> </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_c78c027e9d6e42208753bbb36f814d01" contextRef="c20231231_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>

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  <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_4d92507d58274c9db2aa440013bf07e2" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">44.5</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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    <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_883eaa0df6fa4d2d816fd85b73a73d01" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.2</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

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    <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_5c75d58f5a434990850c3cf960d7b0c3">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; width: 88%;">
          <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; 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:DebtInstrumentInterestRateStatedPercentage" id="Fact_0f525a8c9800435d95eaac252a0ae748" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</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: top; width: 88%; 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; 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:DebtInstrumentInterestRateEffectivePercentage" id="Fact_0031227931764590b83639c1dd2435bb" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </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_62cf1ad5dc7c480c96f00ab044c2cb4a" contextRef="c20231231_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_230a6783f6d947ddbba6d43025cfdeb9" contextRef="c20231231_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, excluding shares related to <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e3f2cb5fe17648b7b0f6f581d37f2b52" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></span>% Notes we have repurchased and are currently holding in treasury</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_72497f617ee44ff3ba52eaf02f2f9feb" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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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_3bc795c421da420da2a22d5537147977" contextRef="c20231231_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 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_a9e68e18a66c490cbd4de10065e4d2e7" contextRef="c20231231_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_7c1fa536b119496284ec81c1d2ec66af" contextRef="c20231231_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_ee1e2d9a0d4f40bda889e2d414ca53ec" contextRef="c20231231_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_547f7d199ac54559bb26fec15121cc0c" contextRef="c20231231_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_e07ddcba2c40439aa143adc7ec803e5c" contextRef="c20190101to20191231_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_c14c01070e90448bb668496d2df0b9da" contextRef="c20190101to20191231_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_187977c4a1dc4ec9884c191c74f41f85" contextRef="c20191001to20191231_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_0b2f9f1a5a8a4bac919a9df86ccfd20b" contextRef="c20231231_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_2f842b01ff1046c3b87d49c91dbe97c9" contextRef="c20231231_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_ae172880ec1c46c0af9cd576a88b5944" contextRef="c20231231_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 </span><span style="-sec-ix-hidden:Fact_b2783015cbc64323aab97584a4bd55af">December 2024</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. 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_ea7c588bbe6348e2bc83429f14bfe7d9" contextRef="c20231231_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_e36b3434d50243eebc6487c0d49766c0" contextRef="c20231231_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 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: 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_e1b4f4155f854dd78c5c594e31875bca" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>%, <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_82f1ae3649ac4b75a4132dc445074f98" contextRef="c20231231_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_64b7f72ab68740679f2224b1bbcd947d" contextRef="c20231231_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_aa349f82e3cf4baf85bc7cd848b5ff63" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_3fe074289f584cb4b560a30997a0ea2c" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_1f213cc402294f1ca4026884343497ac" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction></ix:nonFraction></ix:nonFraction> percent of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.</div>
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<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, 2023, 2022 and 2021 included $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_05fac467f34b4325a9b3a4217145b9d9" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.9</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_04b89c3ed7cd436b93a1c06d91163c41" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.3</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_88e0ec7ba1354b8fb9319b06199da578" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.9</ix:nonFraction> million, respectively, of
    non-cash interest expense related to the amortization of debt issuance costs for our convertible notes.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Financing Arrangements</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;">Operating Facilities</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2017, we purchased the building that houses our primary R&amp;D facility for $<ix:nonFraction name="us-gaap:PaymentsToAcquireBuildings" id="Fact_4a0c024b965c4f51b897f9cf5bc80424" contextRef="c20170101to20171231_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="c20170101to20171231_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="c20170101to20171231" unitRef="U017" 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="c20171231_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="c20171231_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="c20171231_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="c20230101to20231231_DebtInstrumentAxis_ManufacturingFacilityMortgageMember" format="ixt-sec:durwordsen"><ix:nonNumeric name="ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" id="Fact_885a5330a5d64c1ca25849873c2df457" contextRef="c20230101to20231231_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 2022 in conjunction with a sale and leaseback transaction.</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec756" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec757">
<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 2022, we concurrently entered into <ix:nonFraction name="ions:NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" id="Fact_8733f15524b344938a5622966d91cd3f" contextRef="c20220101to20221231" unitRef="U018" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction>
    purchase and sale agreements with a real estate investor. In the same period, we closed the first transaction in which we sold the facilities at our headquarters in Carlsbad, California, which includes our primary R&amp;D facility, for a purchase price
    of $<ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_995ff98913014ef6a5f5fc51445c7128" contextRef="c20220101to20221231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">263.4</ix:nonFraction> million. As a result, we de-recognized the related land and improvements, building and building improvements, which resulted in a net
    gain of $<ix:nonFraction name="us-gaap:GainLossOnDispositionOfAssets1" id="Fact_e1b424eff905493698bc9b6f4316f08f" contextRef="c20220101to20221231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">150.1</ix:nonFraction> million that we reported in other income in our consolidated statements of operations. 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="c20220101to20221231_DebtInstrumentAxis_PrimaryResearchAndDevelopmentFacilityMortgageMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">51.3</ix:nonFraction> million. In connection with this transaction, we leased back
    our headquarters facilities for an initial lease term of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_e6d37e165f84425ea9db0bd0fa02c2cf" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" format="ixt-sec:duryear">15</ix:nonNumeric> years with options to extend the lease for <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_0746b48df37641eaab4f8443ed332073" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U020" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> additional terms of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_693e91d48d5b4feebec724ed9ff884f7" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" format="ixt-sec:durwordsen">five years</ix:nonNumeric> each.</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec758" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec759">
<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 August 2023, we closed the second transaction and transferred legal ownership of <ix:nonFraction name="ions:NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" id="Fact_a8c5588ea2e04cc99ff52c8cb117bb7b" contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_LandMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> lots of undeveloped land adjacent to our headquarters to the real estate investor for a purchase price of $<ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_c3af5a38042e409fa61183221c638107" contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_LandMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">33</ix:nonFraction> million. In connection with this transaction, we entered 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 R&amp;D and office 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_e198dab14cc74d2fadbd634160d04423" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" format="ixt-sec:duryear">15</ix:nonNumeric> years with options to extend the lease for <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_23a41853ffc14bdb96e6c3de4058ab3a" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" unitRef="U020" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> additional terms of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_782a866aae5e44f4a70dc6a5aa6bd1b5" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" format="ixt-sec:durwordsen">five years</ix:nonNumeric> each. The lease will commence once the structure of this new facility is completed.</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;">Since the building is under construction and unavailable to lease, we are unable to complete the sale-leaseback evaluation under ASC 842,
    Leases. As a result, the land remains in our consolidated balance sheets and we accounted for the proceeds as a financial liability. We will reassess the transaction under the sale-leaseback accounting guidance when the facilities are available for
    lease commencement.</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec762" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec763">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Debt Maturity Schedules</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec764" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec765"><ix:nonNumeric name="srt:ContractualObligationFiscalYearMaturityScheduleTableTextBlock" id="Text_16539426e6924191b5cc465550dba8af" contextRef="c20230101to20231231" escape="true" continuedAt="Text_00ff1269eb2340e59b4e4ade440708611">
<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, 2023 are as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec765" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec766"><ix:continuation id="Text_00ff1269eb2340e59b4e4ade440708611" continuedAt="Text_00ff1269eb2340e59b4e4ade440708612">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec766" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec767"><ix:continuation id="Text_00ff1269eb2340e59b4e4ade440708612">
<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;">2024</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">55,298</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;">2025</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,657</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;">2026</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">643,157</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;">2027</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,509</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;">2028</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">580,277</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,462</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,308,360</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: 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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">157</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">47,138</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,061</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <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 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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,241,004</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: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-36</div>

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<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 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="c20231231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadFacilityMember" unitRef="U020" 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="c20231231_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 an additional office space and warehouse space in Carlsbad. We lease these spaces under non-cancelable operating leases. In
    2022, we exercised our option to extend the office space lease, extending our term from January 2023 to May 2027. We have <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_fda06318ab41423f9e871d23c3ba6480" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadOfficeSpaceMember" unitRef="U020" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> remaining options
    to extend this lease. Our warehouse space lease in Carlsbad has an initial term ending in 2028 with <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_08797d9de1754a398e2476e465a5a05d" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadWarehouseSpaceMember" unitRef="U020" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> options to extend the lease.</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 2022. The initial lease term for our headquarters facilities is <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_7f2058c8172e474bbf205fda14546132" contextRef="c20231231_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="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U020" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction>
    additional terms of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_1488c1954cd849a1a4f6161cf2b82691" contextRef="c20231231_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="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">280</ix:nonFraction> million. In connection with the
    transfer of legal ownership of the <ix:nonFraction name="ions:NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" id="Fact_17aadca36cd14bb7b824374f744e4abc" contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> lots of undeveloped land to the real estate investor, we entered 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. The lease will commence once the structure of this new facility is completed.</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 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility to be constructed by
    the lessor in Oceanside, California. We capitalized costs that we incurred related to the design and development of tenant improvements as construction-in-progress in our consolidated balance sheets. In August 2023, we reached a mutual agreement with
    the lessor to terminate the lease agreement. As a result, we recorded a charge of $<ix:nonFraction name="us-gaap:ImpairmentOfLongLivedAssetsHeldForUse" id="Fact_171f16cc89494c4ea4ec3ca4d9a325d8" contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction> million, primarily associated with the impairment of
    construction-in-progress assets, within <span style="-sec-ix-hidden:Fact_ebdf1ed5cf6845079198439e7c520f42">SG&amp;A expense</span> in our consolidated statements of operations.</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="c20231231_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="c20231231_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="c20230101to20231231_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 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="c20231231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember" format="ixt-sec:durmonth">83</ix:nonNumeric> months following the sublease commencement date with <ix:nonFraction name="ions:LessorOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_8c1775b36c92469e9d8ba3d06078efc9" contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember" unitRef="U020" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> option to extend the
    sublease. Under the sublease agreement we provided a <ix:nonNumeric name="ions:LessorOperatingLeasePeriodOfFreeRent" id="Fact_bdb3d42dbeaf484494c12e827a769a24" contextRef="c20230101to20231231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember" format="ixt-sec:durwordsen">seven-month</ix:nonNumeric> free rent period, which commenced in January 2022. We will receive lease
    payments over the sublease term totaling $<ix:nonFraction name="us-gaap:LessorOperatingLeasePaymentsToBeReceived" id="Fact_7c8de04d910848adb798d3e411c0825d" contextRef="c20231231_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="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 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="c20231231_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="c20231231_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="c20230101to20231231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember" format="ixt-sec:durwordsen">seven-month</ix:nonNumeric> free rent period, which commenced in November 2021. Our lease payments over the
    initial term total $<ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue" id="Fact_c350c485d2194852998ea1b496903ff5" contextRef="c20231231_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="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 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; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At December 31, 2023</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>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAsset" id="Fact_42b72db309654cf1bdbfe546a3a2176d" contextRef="c20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">171.9</ix:nonFraction></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;">Operating 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:OperatingLeaseLiability" id="Fact_44caa1523d334df48c7b2561738097e4" contextRef="c20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">179.0</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="c20231231" format="ixt-sec:duryear">13.0</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="c20231231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">6.9</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>


</table>
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  </div>
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  <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;">F-37</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>
<div><ix:continuation id="Text_d3f9b7e5460e4829b7b257421c67d80428" continuedAt="Text_d3f9b7e5460e4829b7b257421c67d80429">
<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, 2023,
    2022, and 2021 we paid $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_826cead5743b4e90a9d8b807e97fe422" contextRef="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">20.1</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_297fcce7f2e44b348fe63e7be360cf7c" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.0</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_50e928616e964a8c94f28d1e4409995c" contextRef="c20210101to20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.3</ix:nonFraction> million of lease payments, which were included in operating activities in our consolidated statements of cash flows.</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;">As of December 31, 2023,
    the future payments for our operating lease liabilities are as follows (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; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" 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;">2024</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,398</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;">2025</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,645</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;">2026</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="c20231231" 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%; 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;">2027</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="c20231231" 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%; 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;">2028</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,774</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">176,138</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">279,536</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">100,567</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,094</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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">170,875</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_d3f9b7e5460e4829b7b257421c67d80433" continuedAt="Text_d3f9b7e5460e4829b7b257421c67d80434">
<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_d3f9b7e5460e4829b7b257421c67d80434">
<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="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.1</ix:nonFraction> million,
    $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_37e7125f4da2437a81d1b7f1853e4554" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.3</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_a6f37ce5e1654e67b6bfb04f2bfaa94b" contextRef="c20210101to20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.4</ix:nonFraction> million for the
    years ended December 31, 2023, 2022
    and 2021, respectively. </div>
</ix:continuation></div>


  <div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> <br/>
    </div>
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    <ix:continuation id="Text_1e6cd6cf7156470da11a49cfddf68ec768" continuedAt="Text_1e6cd6cf7156470da11a49cfddf68ec769">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Royalty Revenue Monetization</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="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" 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" 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" 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" 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" 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" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of
    any future royalty payments on pelacarsen. 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" 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" 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.</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 upfront payment of $<ix:nonFraction name="ions:UpfrontRoyaltyPaymentReceived" id="Fact_f0e73629c96a44169a5a0e9d8a1d4b9a" contextRef="c20230101to20230131" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">500</ix:nonFraction>
    million as a liability related to the sale of future royalties, net of transaction costs of $<ix:nonFraction name="ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_1391ba32fa9a456194c1aa68413d1b61" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.4</ix:nonFraction> million, which we are amortizing over the
    estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty
    Pharma as a reduction of the liability.</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 determine the effective interest rate used to record
      interest expense under this agreement based on an estimate of future royalty payments to Royalty Pharma. As of </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the estimated effective interest rate under the agreement was </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_d7d548cc748640208f68b9bf1f4a17e2" contextRef="c20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">13.5</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</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;">The following is a summary of our liability related to
      sale of future royalties for the year ended </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (in thousands):</span></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: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of future 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="ions:ProceedsFromSaleOfFutureRoyalties" id="Fact_b900ad354383483f9c34ba3b6c879d07" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">500,000</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;">Royalty payments to Royalty Pharma</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:RoyaltyPayments" id="Fact_67ccd0c0a7a24a5f910faba6121087a7" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">44,628</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: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</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:InterestExpenseRelatedToSaleOfFutureRoyalties" id="Fact_a9cc1712c3f242eb9a739d51e13366c1" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">68,238</ix:nonFraction></div>
        </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>

  </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;">Liability related to sale of future royalties as of December 31, 2023</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:LiabilityRelatedToSaleOfFutureRoyaltiesGross" id="Fact_421502ea384841d691af85563752cb84" contextRef="c20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">523,610</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance costs related to sale of future 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">&#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:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" id="Fact_1644e2bd10d14c018b1fdb09c827c31a" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,434</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: 88%; padding-bottom: 2px;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties as of December 31, 2023</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:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_99010a2025d14f9695d7f43cbc7feb2d" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">560</ix:nonFraction></div>
        </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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of December 31, 2023</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:LiabilityRelatedToSaleOfFutureRoyaltiesNet" id="Fact_c74c6b7b6d844b66867bedb3fe98aa1a" contextRef="c20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">513,736</ix:nonFraction></div>
        </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">&#160;</td>

  </tr>


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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty
    payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the commercial sales of SPINRAZA, the regulatory approval and commercial sales of
    pelacarsen, competing products or other significant events.</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;">F-38</div>

    </div>

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    <div class="BRPFPageHeader">
      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

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<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;">8. Stockholders</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> Equity</span></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Preferred Stock</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="c20231231_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, 2023, there were <ix:nonFraction name="us-gaap:PreferredStockSharesOutstanding" id="Fact_9e3c83d35b1a4ad9bb5804db20a70950" contextRef="c20231231_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="c20231231_StatementClassOfStockAxis_SeriesCPreferredStockMember" unitRef="U002" decimals="INF" scale="0" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:PreferredStockSharesIssued" id="Fact_5fe1b66991274e8cbc8b7286eae05354" contextRef="c20231231_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, 2023.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">At December 31, 2023 and 2022, we had <ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_292edcba897f40209ed42c14feed0f2e" contextRef="c20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_10c668f50b664401a30c1bb6a51edb5a" contextRef="c20231231_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="c20231231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_5f23b4a620974ffa9ac1338867c08a09" contextRef="c20231231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">144.3</ix:nonFraction></ix:nonFraction> million and <ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_eba69077d17e4204b64b00ee384f8ab0" contextRef="c20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_7461dbbf5e58485bbd613618075e0ee5" contextRef="c20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">142.1</ix:nonFraction></ix:nonFraction> million were issued and outstanding, respectively. As of December 31, 2023,
    total common shares reserved for future issuance were <ix:nonFraction name="us-gaap:CommonStockCapitalSharesReservedForFutureIssuance" id="Fact_47e88bfdb1664c48a2b1ff64f80389f5" contextRef="c20231231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">49.7</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, 2023,
    2022 and 2021, we issued <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_0ee4b00a77834001bc604428d95159c5" contextRef="c20230101to20231231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.3</ix:nonFraction> million, <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_6d8eb059ce834187b603ca07d5abb207" contextRef="c20220101to20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.2</ix:nonFraction> million and <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_edd10ce23a74492e8176afb94a7abdb0" contextRef="c20210101to20211231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.1</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="c20230101to20231231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">49.4</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_5fbad294b6304ae4a8a72a7d07384a09" contextRef="c20220101to20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.4</ix:nonFraction>
    million and $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_4af5fbc849034e59b7d2901adc45af29" contextRef="c20210101to20211231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">11.6</ix:nonFraction> million in 2023,
    2022 and 2021, respectively.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock Plans</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 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="c20231231_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 Stock Option Plan, or 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="c20230101to20231231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period, with <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_816b79e6c6644c99b9269bf591370d3f" contextRef="c20230101to20231231_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="c20230101to20231231_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="c20230101to20231231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric>. At December 31, 2023, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_aac422de44984b5691b8963611354e87" contextRef="c20231231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-3" scale="3" format="ixt-sec:numwordsen">no</ix:nonFraction> options were outstanding and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_8c931ba74e0d4e5c8d57ed4b294c4a22" contextRef="c20231231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">68</ix:nonFraction>,000 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 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 June 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>In June 2023, after receiving approval from our stockholders, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2011 Plan to increase 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_441bcd9f19644c13947731bccdf147fa" 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 to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_fdc58c93dda24d23a21b330e207c7f2c" contextRef="c20230630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">35.2</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million.</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 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="c20230101to20231231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period, with <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_13d5cd5cb0eb4f0e964e186051bcf7a9" contextRef="c20230101to20231231_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="c20230101to20231231_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="c20230101to20231231_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="c20230101to20231231_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="c20230101to20231231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. At December 31, 2023, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_f6eb4ef69d9549b79f43b5ca7f3d3f65" contextRef="c20231231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">12.8</ix:nonFraction> million
    options were outstanding, of which <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_c37dd0f781d649a5bc97d2c87bbaeacf" contextRef="c20231231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.7</ix:nonFraction> million were exercisable, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber" id="Fact_f19dff70c85e4b53ab5b44f7e4b872f2" contextRef="c20231231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.3</ix:nonFraction> million restricted stock unit awards were outstanding, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_f121d278af9942b4ba6d23912dbef6db" contextRef="c20231231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.0</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="c20230101to20231231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U021" 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="c20230101to20231231_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">three months</ix:nonNumeric> before and ends <ix:nonNumeric name="ions:PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" id="Fact_4b4db5c64d7f42eca6f341535cd62db4" contextRef="c20230101to20231231_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 2020, we assumed the
      unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In 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="c20230101to20231231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period, with <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_bf4c2072cc4b4282835c60cb240d0d17" contextRef="c20230101to20231231_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="c20230101to20231231_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="c20230101to20231231_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="c20230101to20231231_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="c20230101to20231231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. At December 31, 2023, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_7b23f3391b8648699d7f9d9bdfc98ad2" contextRef="c20231231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.4</ix:nonFraction> million
    options were outstanding, of which <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_6b4dbdd5c0164b6fb94f3a918f49204a" contextRef="c20231231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction> million were exercisable, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber" id="Fact_998c6813ad25478d8df2ef4e673ad903" contextRef="c20231231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.2</ix:nonFraction> million restricted stock unit awards were outstanding, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_445e0eb67023409bac8ed8d6e705c2d6" contextRef="c20231231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.0</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
            acquiring corporation (or its parent company);</div>
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          <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>
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          <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>
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          <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>
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          <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>
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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;">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 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 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="c20141231_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="c20151231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.0</ix:nonFraction> million. In 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 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="c20151231_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="c20201231_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>
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          <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>
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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;">A revision to the vesting schedule of new awards granted; and</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 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="c20230101to20231231_AwardTypeAxis_StockOptionMember_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" format="ixt-sec:durwordsen">10 years</ix:nonNumeric>
    from the date of grant. At December 31, 2023, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_28beff5bd3d14e0c9936c3a0e4bfd184" contextRef="c20231231_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="c20231231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.9</ix:nonFraction> million were exercisable, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber" id="Fact_52cd031e53a5493d8ae9f30994d9f850" contextRef="c20231231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">40</ix:nonFraction>,000 restricted stock unit awards were outstanding, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_03da27efb55141628520731fb9e70ab8" contextRef="c20231231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.5</ix:nonFraction>
    million shares were available for future grant under the 2002 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: -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 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_58982d3bd4cb40b3bbb0b5a03017f488" contextRef="c20090101to20091231_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_e15dcdc6c66e42559a10c287b0c7cf55" contextRef="c20180101to20181231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_cacfad7964034bbcaca2399bf5f2cb59" contextRef="c20150101to20151231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_c4b9f36e104042d497da7d7c2821b9f9" contextRef="c20140101to20141231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_c241e58357d3452dbf7f5a5a59d22102" contextRef="c20130101to20131231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_a4221b1732584bdab68ea669d5dbfe57" contextRef="c20110101to20111231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_9d75e90a44af478cbe373b16a80b30bf" contextRef="c20190101to20191231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_55052c57d9944f4597bc1762f9393ed7" contextRef="c20170101to20171231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_465d86e4aca54bf99fa8576d3a113eb5" contextRef="c20160101to20161231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_1a5a7e2d42b24fe5bbdd8eb2e9ed40a3" contextRef="c20120101to20121231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_199329985b3f4b9a93a30c0aba085d4e" contextRef="c20100101to20101231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">150,000</ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction></ix:nonFraction> shares of common stock for the ESPP resulting in a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_38cefc5306ef4b91b96aa796ece9f65c" contextRef="c20231231_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, 2023. The ESPP
    permits full-time employees to purchase common stock through payroll deductions (which cannot exceed <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" id="Fact_cde6d0b8308541d399ef173d781f45db" contextRef="c20231231_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_194baea1b26142beaba2816576b72b95" contextRef="c20230101to20231231_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_c0a6d71bb09f40b8b835538d12005c8d" contextRef="c20230101to20231231_PlanNameAxis_EmployeeStockPurchasePlanMember" format="ixt-sec:durwordsen">six months</ix:nonNumeric> from the date of purchase. During 2023, employees purchased and we issued to employees <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" id="Fact_28531580c1b34f999f1b8c754d078864" contextRef="c20230101to20231231_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_19161be6484c4f6f96fdfb2dbfaf9342" contextRef="c20230101to20231231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">30.53</ix:nonFraction> per share. At December 31, 2023, there were <ix:nonFraction name="ions:EmployeeStockPurchasePlanSharesAvailableForPurchase" id="Fact_d43712676b7c40d4972a35e470cb8c41" contextRef="c20231231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.4</ix:nonFraction> 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 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, 2023 (in thousands, except per share and contractual life data):</div>
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<div><br/>
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    <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; white-space: nowrap;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</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>

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          <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; white-space: nowrap;" 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; white-space: nowrap;" 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, 2022</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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_de361e6a303f48689eff997a4c7a9e18" 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; 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>
        </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:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" id="Fact_013443363d8b4eb7aa061c464dc7a3dd" 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; 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;">
          <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;" 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>

    <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="c20230101to20231231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">38.80</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="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="c20230101to20231231_AwardTypeAxis_StockOptionMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,444</ix:nonFraction></div>
        </td>

    <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>
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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>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 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="vertical-align: bottom; text-align: right; padding-bottom: 2px;" colspan="1">
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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;" 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>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;">
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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">&#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>

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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 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%; 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">
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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%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 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>

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    <td valign="bottom" style="vertical-align: bottom; width: 52%; 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%; 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">&#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">
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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%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 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%; 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="c20231231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,349</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>

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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;">The weighted-average estimated fair values of options granted were $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_bd436c790ccc47e68cd7e2153d0e63dd" contextRef="c20230101to20231231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">19.72</ix:nonFraction>, $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_4dd2a593ab554175bbb0a93d55390a88" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">18.66</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_a3befa246b7c4d03aced2b483085120f" contextRef="c20210101to20211231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">24.35</ix:nonFraction> for the years ended December 31, 2023, 2022 and 2021, respectively. The total intrinsic value of options
    exercised during the years ended December 31, 2023, 2022 and 2021 were $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_1218d40eea68418bb4f00f1ad78f4cff" contextRef="c20230101to20231231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.0</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_bde2c92764604d8497b0668d13fb888b" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.4</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_8cc0e16daa8e4b2382fc554cc98ddf99" contextRef="c20210101to20211231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.5</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="c20230101to20231231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">65.1</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ProceedsFromStockOptionsExercised" id="Fact_9199ba163c904e0aaa3d539cccdda650" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.6</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ProceedsFromStockOptionsExercised" id="Fact_6cc972e2025849d8a6820145ab793c87" contextRef="c20210101to20211231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.5</ix:nonFraction> million for the years ended December 31, 2023, 2022 and 2021, respectively. For the year
    ended December 31, 2023, the weighted-average fair value of options exercised was $<ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" id="Fact_2b17593a26f3421991429bedce8b1c41" contextRef="c20230101to20231231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">49.23</ix:nonFraction>. As of December 31, 2023, total unrecognized compensation cost related to
    non-vested stock options was $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" id="Fact_72c37b7b47114b45a9abf8d6722faa52" contextRef="c20231231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">36.6</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="c20230101to20231231_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 class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-41</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>
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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 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, 2023 (in thousands, except per share data):</div>
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    <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>
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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>

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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>
          <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>
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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;"><span style="text-indent: 0pt;">Non-vested at December 31, 2022</span></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>

    <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: 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>

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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">
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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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; 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 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">
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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;">
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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">
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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%; 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="c20230101to20231231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">42.90</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, 2023</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="c20231231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,239</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="c20231231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">43.40</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>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_cff6a726aed441b1beca6a648e25be1473" continuedAt="Text_cff6a726aed441b1beca6a648e25be1474">
<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_cff6a726aed441b1beca6a648e25be1474" continuedAt="Text_cff6a726aed441b1beca6a648e25be1475">
<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, 2023,
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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>
</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;">The following table summarizes the PRSU activity for the year ended December 31, 2023 (in thousands, except per share data):</div>
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<div><br/>
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    <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>
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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; white-space: nowrap;" 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;">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>
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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; 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;">Non-vested at December 31, 2022</span></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">
          <div style="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:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" id="Fact_89dc0084c002439b8e4a0538481494ee" 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%; 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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">
          <div style="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:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_e98c02aa77564502bd9487c4f288a2e3" contextRef="c20230101to20231231_AwardTypeAxis_PerformanceSharesMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">57.43</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</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="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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

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  <tr>

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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>

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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>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

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</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_cff6a726aed441b1beca6a648e25be1481" continuedAt="Text_cff6a726aed441b1beca6a648e25be1482">
<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_cff6a726aed441b1beca6a648e25be1482" continuedAt="Text_cff6a726aed441b1beca6a648e25be1483">
<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, 2023,
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</ix:continuation>
  <ix:continuation id="Text_cff6a726aed441b1beca6a648e25be1483" continuedAt="Text_cff6a726aed441b1beca6a648e25be1484">
<div><br/>
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</ix:continuation>
  <ix:continuation id="Text_cff6a726aed441b1beca6a648e25be1484" continuedAt="Text_cff6a726aed441b1beca6a648e25be1485">
<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>
</ix:continuation>
  <ix:continuation id="Text_cff6a726aed441b1beca6a648e25be1485" continuedAt="Text_cff6a726aed441b1beca6a648e25be1486">
<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;">The following table summarizes stock-based compensation expense for the years ended December 31, 2023, 2022 and 2021 (in thousands):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_cff6a726aed441b1beca6a648e25be1487" continuedAt="Text_cff6a726aed441b1beca6a648e25be1488"><ix:continuation id="Text_fb79054e03b84db7a6e42d6c2a6527151" continuedAt="Text_fb79054e03b84db7a6e42d6c2a6527152">
<div><br/>
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</ix:continuation></ix:continuation>
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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>

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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;">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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    <td valign="bottom" style="vertical-align: bottom; width: 1%; 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>

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  <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;">Research, development and patent</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:AllocatedShareBasedCompensationExpense" id="Fact_082a856e25ff4c6c87bb43e07011a3a0" contextRef="c20230101to20231231_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">77,826</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:AllocatedShareBasedCompensationExpense" id="Fact_fbf019d0d38c4d20951785656bdfb76e" contextRef="c20220101to20221231_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">73,704</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:AllocatedShareBasedCompensationExpense" id="Fact_590dd7d3580e4ce79e0bd853a27c60e2" contextRef="c20210101to20211231_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">87,522</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: 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_faf4608623c94854a015ec45e8a2e44a" contextRef="c20230101to20231231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,484</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:AllocatedShareBasedCompensationExpense" id="Fact_e2891cabb204471380d6c8707ca7c311" contextRef="c20220101to20221231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">26,027</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:AllocatedShareBasedCompensationExpense" id="Fact_1d43b8c463a34284a11803d822ccf283" 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>

  </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</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="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">105,809</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:AllocatedShareBasedCompensationExpense" id="Fact_e09ed4e35f1149ffade548f4d1e3dd6a" 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>

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          <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;">Refer to 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>
</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;">F-42</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </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 the years ended December 31, 2023,
    2022 and 2021, we used the
    following weighted-average assumptions in our Black-Scholes calculations:</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;">Employee Stock Options:</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; 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">&#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: 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>

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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: 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;">Volatility</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="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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>
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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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  </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 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>

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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>

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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="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;">Board of Director Stock Options:</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="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;">2023</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;">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">
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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="vertical-align: bottom; width: 1%; background-color: #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>

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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: 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;">Volatility</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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  <tr>

    <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>

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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>

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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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    <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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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</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;">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; 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>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" id="Fact_d445da93ea354d4a8bd3403324c38b1b" contextRef="c20220101to20221231_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">1.2</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">
          <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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" id="Fact_7e683d90439c433b952d511d85e1a926" contextRef="c20210101to20211231_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.1</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>

    <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>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_0eb7e7fbc4304fdf9099a8b950d12dde" contextRef="c20220101to20221231_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.0</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_34e237d15deb4d56bee7e4f7c1e34d34" contextRef="c20210101to20211231_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.0</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>

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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;">Volatility</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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate" id="Fact_46d7ebf746c644dbab44800478c4bf2c" contextRef="c20210101to20211231_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">42.4</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;">
          <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_6cb5a0bf099e40cc864c264a7ce21cef" contextRef="c20230101to20231231_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durwordsen">6 months</ix:nonNumeric></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="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_f4dc66b6347f46f7b1f589a4102dcbc3" contextRef="c20220101to20221231_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durwordsen">6 months</ix:nonNumeric></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="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>
</ix:continuation>
  <ix:continuation id="Text_cff6a726aed441b1beca6a648e25be14106" continuedAt="Text_cff6a726aed441b1beca6a648e25be14107">
<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>
  <ix:continuation id="Text_cff6a726aed441b1beca6a648e25be14108" continuedAt="Text_cff6a726aed441b1beca6a648e25be14109">
<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_cff6a726aed441b1beca6a648e25be14110" continuedAt="Text_cff6a726aed441b1beca6a648e25be14111">
<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_cff6a726aed441b1beca6a648e25be14112" continuedAt="Text_cff6a726aed441b1beca6a648e25be14113">
<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="c20230101to20231231_AwardDateAxis_IssuedAfterDecember312021Member_AwardTypeAxis_EmployeeStockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_c4148e9887894ea9af96e0d8258b9049" contextRef="c20230101to20231231_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 years ended December 31, 2023 and 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_cff6a726aed441b1beca6a648e25be14114">
<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>
</ix:continuation></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;">F-43</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </div>

  </div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:IncomeTaxDisclosureTextBlock" id="Text_6df02471ad074e68b7de0becddf8a447" contextRef="c20230101to20231231" escape="true" continuedAt="Text_1ce9ae82520d4ac38cf746525525322b1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">9. Income Taxes</div>
</ix:nonNumeric>

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  </div>
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  <ix:continuation id="Text_1ce9ae82520d4ac38cf746525525322b2" continuedAt="Text_1ce9ae82520d4ac38cf746525525322b3"><ix:nonNumeric name="us-gaap:ScheduleOfIncomeBeforeIncomeTaxDomesticAndForeignTableTextBlock" id="Text_7281bd0eb54443b994694c659a6a8f66" contextRef="c20230101to20231231" escape="true" continuedAt="Text_cf23b3c75380420fa8a39f45d9dc5a7b1">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss before income taxes is comprised of (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">


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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;">2023</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;">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: 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>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; 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_1154d9477ea5403c89bcaba61b591e79" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">334,707</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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic" id="Fact_74d3abad4f744e0aa68801acc3a6ed6b" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">258,493</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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic" id="Fact_8977ca2c8272434794efd8259c5f22b7" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">29,966</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: 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign" id="Fact_70ca994a31be49619caefe5e71de1587" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">742</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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign" id="Fact_8425f2adaf6948cdb4db61cdf7def1fc" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">508</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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign" id="Fact_15eeca6092a14a5c9b839eb716ea8ae4" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">818</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;">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">
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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>
        </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">
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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">
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  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_1ce9ae82520d4ac38cf746525525322b5" continuedAt="Text_1ce9ae82520d4ac38cf746525525322b6">
<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;">Our income tax expense (benefit) was as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation>
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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;">2023</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;">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>

  </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>
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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: 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>
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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:CurrentFederalTaxExpenseBenefit" id="Fact_f7d1c022ad9f48ddaa94094db5e10a09" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">35,861</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:CurrentFederalTaxExpenseBenefit" id="Fact_3b8dd023e1f647b8a3ac8d6daa73c20c" 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>
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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:CurrentFederalTaxExpenseBenefit" id="Fact_7390edee7ebc486d8f38622d5c52bcc1" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">200</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>

  <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:CurrentStateAndLocalTaxExpenseBenefit" id="Fact_29cdf46cccf847508b045e7ee750b157" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">3,687</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:CurrentStateAndLocalTaxExpenseBenefit" id="Fact_18598915ff304ad69c4f603530fa17ba" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,129</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:CurrentStateAndLocalTaxExpenseBenefit" id="Fact_b16b487bd08b4f16b0833b9f760c9124" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">690</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%; 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="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">147</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="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_94c31631758a4c52bc819107405e16bf" 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>

  </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="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,321</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="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">
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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;">&#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>

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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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredStateAndLocalIncomeTaxExpenseBenefit" id="Fact_e78064ae2d4443f18407baa35f73bf2f" contextRef="c20230101to20231231" 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">&#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="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>

  </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="c20230101to20231231" 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="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_b02665644bb848b5b79ed1b9b7aba937" 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>

  </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="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,321</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="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_72e6d39ff1da4d90b52e886f5e5ff672" 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>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_1ce9ae82520d4ac38cf746525525322b9" continuedAt="Text_1ce9ae82520d4ac38cf746525525322b10">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_1ce9ae82520d4ac38cf746525525322b10" continuedAt="Text_1ce9ae82520d4ac38cf746525525322b11"><ix:nonNumeric name="us-gaap:ScheduleOfEffectiveIncomeTaxRateReconciliationTableTextBlock" id="Text_51a6178b5d104096a200807a70958787" contextRef="c20230101to20231231" escape="true" continuedAt="Text_adc3b68eac4e46fba233ab9c39fe46341">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; 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 loss before income taxes. The sources
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</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_1ce9ae82520d4ac38cf746525525322b11" continuedAt="Text_1ce9ae82520d4ac38cf746525525322b12"><ix:continuation id="Text_adc3b68eac4e46fba233ab9c39fe46341" continuedAt="Text_adc3b68eac4e46fba233ab9c39fe46342">
<div><br/>
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_1ce9ae82520d4ac38cf746525525322b12" continuedAt="Text_1ce9ae82520d4ac38cf746525525322b13"><ix:continuation id="Text_adc3b68eac4e46fba233ab9c39fe46342">
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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="22">
          <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="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2023</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="6">
          <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="6">
          <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; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pre-tax loss</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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_48c8db752dd847f894945e665263db28" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">333,965</ix:nonFraction></div>
        </td>

    <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="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>
        </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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_d90962261a1d4e50b88595c178ff0d7d" 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; 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="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>
        </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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_82f7c2373f9d4876bd0497532436a6c4" 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; 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="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;">
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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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  </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>

    <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">
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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%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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>

  </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;">Foreign</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>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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">
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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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net change in valuation allowance</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>

    <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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  </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">&#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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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">
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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 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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred tax true-up</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">
          <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:EffectiveIncomeTaxRateReconciliationPriorYearIncomeTaxes" id="Fact_7b8114439ec74d04b71a3c5bf7cc21bb" contextRef="c20220101to20221231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.0</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax rate change</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>

    <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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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: 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">&#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;">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 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 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>

  </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;">Foreign-derived intangible income benefit</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>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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">&#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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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; 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">
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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>

    <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 valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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  <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>
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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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxReconciliationOtherAdjustments" id="Fact_579c7a65442043da929eea96c26a5f30" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">405</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>
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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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); 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: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationOtherAdjustments" id="Fact_4c434cf931ee4c45825ee90aa9c5caf0" contextRef="c20220101to20221231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">0.1</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;" colspan="1">
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        </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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxReconciliationOtherAdjustments" id="Fact_bc52c68679ef48cab49f85908463be0f" 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationOtherAdjustments" id="Fact_4d88b363955f43e1a07814eb57337204" 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%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); 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: 4px double rgb(0, 0, 0);" colspan="1">
          <div style="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: 4px double rgb(0, 0, 0);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_deca3f5e839941f4a90d3b8031b558aa" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,321</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: 4px double rgb(0, 0, 0);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateContinuingOperations" id="Fact_5b3403b4768d4be492d67b3c92d9483d" contextRef="c20230101to20231231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">9.7</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); 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: 4px double rgb(0, 0, 0);" colspan="1">
          <div style="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: 4px double rgb(0, 0, 0);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_9706d35248bb454c8a3a3c80240bc33f" 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: 4px double rgb(0, 0, 0);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateContinuingOperations" id="Fact_f0cc7188c05e4808b694a7a38a1291cc" contextRef="c20220101to20221231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">4.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); 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: 4px double rgb(0, 0, 0);" colspan="1">
          <div style="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: 4px double rgb(0, 0, 0);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_05f18d362e2441e2a636fa371d9e87f0" 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: 4px double rgb(0, 0, 0);" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateContinuingOperations" id="Fact_b6d022290a824526a58ab495c81c8422" contextRef="c20210101to20211231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">1.9</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); 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="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;">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>
</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;">F-44</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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;">Significant components of our deferred tax assets and liabilities as of December 31, 2023 and 2022 are as follows (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; 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;">2023</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;">2022</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;">Deferred Tax 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: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net operating loss carryovers</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:DeferredTaxAssetsOperatingLossCarryforwards" id="Fact_f6113dec90244be7a15feeec0e7f99b3" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">77,964</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>

  </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;">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">&#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;">
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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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: 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: 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">
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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;">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">
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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: 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%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; 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:DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" id="Fact_7552c538820b415fa183b42f515e84f9" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">238,738</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:DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" id="Fact_454847e0096740a1b60db473f3a38457" 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%; 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;">Long-term 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">&#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:DeferredTaxAssetsLeasingArrangements" id="Fact_f1bc5ca109b2461198124e062adb4830" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">43,718</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:DeferredTaxAssetsLeasingArrangements" id="Fact_21b8f2ff8dfe4306a563b7b9403bb6ad" 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%; 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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sale of future 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">&#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:DeferredTaxAssetsSaleOfFutureRoyalties" id="Fact_dbb07f37125e48fcb324ad5b7b909a70" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">144,608</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:DeferredTaxAssetsSaleOfFutureRoyalties" id="Fact_b3acd3b9b3474c74b270c8e16b14119e" 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>

  </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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,343</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="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>

  </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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,025,713</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="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>

  </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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,166</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="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>

  </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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">42,007</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="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>

  </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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,910</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>

    <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="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>

  </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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">977,630</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="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>

  </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="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">977,630</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="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>

  </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="c20231231" 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="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>

  </tr>


</table>
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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 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>
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<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="c20230101to20231231" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">169</ix:nonFraction>
    million from December 31, 2022 to December 31, 2023.
    The increase was primarily related to increases in our deferred tax assets for capitalized research and development expenses and sale of future royalties.</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;">At December 31, 2023, we had
    federal and state, primarily California, tax net operating loss carryforwards of $<ix:nonFraction name="us-gaap:OperatingLossCarryforwards" id="Fact_d9f8be4484bf4eb29dfdbd375c201523" contextRef="c20231231_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="c20231231_IncomeTaxAuthorityNameAxis_CaliforniaFranchiseTaxBoardMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">398.8</ix:nonFraction> million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2032. At December 31, 2023, we also had federal and California research and development tax credit carryforwards of $<ix:nonFraction name="us-gaap:TaxCreditCarryforwardAmount" id="Fact_895e697c597d405a96e760deb75e2c01" contextRef="c20231231_IncomeTaxAuthorityNameAxis_InternalRevenueServiceIRSMember_TaxCreditCarryforwardAxis_ResearchMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">169.7</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:TaxCreditCarryforwardAmount" id="Fact_8191e961253a4f2faaff06f7920ca14f" contextRef="c20231231_IncomeTaxAuthorityNameAxis_CaliforniaFranchiseTaxBoardMember_TaxCreditCarryforwardAxis_ResearchMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">124.4</ix:nonFraction> million, respectively. Our federal research and development
    tax credit carryforwards will begin to expire in 2038. Our California research and development tax credit carryforwards are available indefinitely. Our 2023 current tax expense includes a benefit of approximately $<ix:nonFraction name="ions:OperatingLossCarryforwardsUtilized" id="Fact_271f5968c6244447b08b477d28f4b2d1" contextRef="c20230101to20231231_IncomeTaxAuthorityAxis_StateAndLocalJurisdictionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.2</ix:nonFraction> million related to utilization of state tax loss carryforwards, primarily California.</div>
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<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>
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<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>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-45</div>

    </div>

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      <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

    </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;">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>
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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; 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;">2023</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;">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: 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="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%; 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>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; 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>

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  <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">
          <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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations" id="Fact_6152a6544b8f4685b14436ee97f6ce58" 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>

  </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;">Decrease 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:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" id="Fact_3f06e5d0f5b747c280280e9fcf69a448" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">737</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:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" id="Fact_39287cd4b49c44a4a617144fa53df1bf" 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%; 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:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" id="Fact_0bb19795798b4cca8d22978a26340bd0" 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%; 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;">Increase 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:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" id="Fact_ecf1724d9d65437ab5ccd486d8ab6ebd" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">429</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:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" id="Fact_0ad407c0955648c48850ba2d8d052462" 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%; 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:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" id="Fact_7d0ea3f6a325421b85ab3cbb04eb12fa" 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%; 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;">Increase for current period tax positions</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:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" id="Fact_6119186f5d854118b836ddc5c481ef2d" contextRef="c20230101to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,032</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:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" id="Fact_f3e7b13433a84e72a642c54ecc6a02b3" 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; 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:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" id="Fact_809af95107674a60b9a6aa50165e5ba7" 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; 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;">Ending balance of unrecognized tax benefits</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:UnrecognizedTaxBenefits" id="Fact_c2747640a25a483791181f56caf8bc45" contextRef="c20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">43,298</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:UnrecognizedTaxBenefits" id="Fact_58382ea6463045ef8f7cefb3fdbf3dd7" 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; 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:UnrecognizedTaxBenefits" id="Fact_ed1574437d194d92b955e24fdec9efce" 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; 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/>
  </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;">Included in the balance of unrecognized tax benefits at December 31, 2023, 2022 and 2021 was $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" id="Fact_552285171ef248dfab36d0ee9948271e" contextRef="c20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.3</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" id="Fact_609bbfafde0b4ea9bce0bad6399c9eb6" contextRef="c20221231" 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="c20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.2</ix:nonFraction> million respectively, that if we recognized, could impact our
    effective tax rate, subject to our remaining valuation allowance.</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 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="c20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.6</ix:nonFraction> million within the next 12 months due to the lapse of statute of limitations on underlying tax positions primarily related to amortization of certain
    capitalized state research and development expenditures.</div>
</ix:continuation>
  <ix:continuation id="Text_1ce9ae82520d4ac38cf746525525322b37" continuedAt="Text_1ce9ae82520d4ac38cf746525525322b38">
<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 recognize interest and/or penalties related to income tax matters in income tax expense. During the years ended December 31, 2023, 2022 and 2021, we recognized $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_5d817f0050924f7f82257fc7b70a23d7" contextRef="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_2955ef1a6fab40d7ab1c8f70571532db" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.8</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_8781f6db0d834e54aff079e85ee20d63" contextRef="c20210101to20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.5</ix:nonFraction> million, respectively, of
    accrued interest and penalties related to gross unrecognized tax benefits.</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;">We are subject to taxation in the U.S. and various state and
      foreign jurisdictions. U.S. tax years 2020 through 2022 remain open to examination and tax years 2019 through 2022 remain open to examination by major state taxing jurisdictions, primarily California, although net operating loss and credit
      carryforwards generated prior to these periods 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</span>.</div>
</ix:continuation></div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:PensionAndOtherPostretirementBenefitsDisclosureTextBlock" id="Text_44a1974bfba9485682c02d2913778f03" contextRef="c20230101to20231231" escape="true" continuedAt="Text_9aa52a99c597469b999bbffbdc78e78c1">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">10. Employment Benefits</div>
</ix:nonNumeric>

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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 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="c20230101to20231231_RangeAxis_MinimumMember" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">22,500</ix:nonFraction> and $<ix:nonFraction name="us-gaap:DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" id="Fact_2703ad6213db4e249c38d0794a2c6418" contextRef="c20230101to20231231_RangeAxis_MaximumMember" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">30,000</ix:nonFraction> in 2023 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="c20230101to20231231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.1</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:DefinedContributionPlanCostRecognized" id="Fact_47a2898dc66b4221ba3a2d92c2c0643a" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.6</ix:nonFraction>
    million and $<ix:nonFraction name="us-gaap:DefinedContributionPlanCostRecognized" id="Fact_0c0b367e1550466b886c0390a13e1e0f" contextRef="c20210101to20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.5</ix:nonFraction> million in matching contributions for the years ended December 31, 2023, 2022 and 2021, respectively.</div>
</ix:continuation></div>

  <div><br/>
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<div><ix:nonNumeric name="us-gaap:LegalMattersAndContingenciesTextBlock" id="Text_656730b2a28e4e958b751e639ff66fd5" contextRef="c20230101to20231231" escape="true" continuedAt="Text_8156a018bc9e463ea4d37432c5df0aee1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">11. Legal Proceedings</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 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;">There are no pending material legal proceedings to which we are a party or of which our property is the subject.</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;">F-46</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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;" href="#TOC">Table of Contents</a></div>

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<div><ix:nonNumeric name="us-gaap:QuarterlyFinancialInformationTextBlock" id="Text_4be6328593df49c295c60f8f5c9d4bc0" contextRef="c20230101to20231231" escape="true" continuedAt="Text_bbe30145442f43ab91936a9d68a84c1e1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">12. 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 2023 and 2022 are as follows (in thousands, except per share data).</div>
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  <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,</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;">2023</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;">2022</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: 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>
        </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:Revenues" id="Fact_284eab838adc45f1bab65fa3ed3e8a21" contextRef="c20231001to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">324,505</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:Revenues" id="Fact_20e60632220f4799962c4c0ff5f00ab5" contextRef="c20221001to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">151,890</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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  <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;">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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_b6f8e9fbc8074a218922e8576d906d68" contextRef="c20231001to20231231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">330,627</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:CostsAndExpenses" id="Fact_ef4a183f40c64bdd8dd30738366a5262" contextRef="c20221001to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">359,909</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;">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;">(<ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_c3c0e5d7387e40eb92385001e70edef5" contextRef="c20231001to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">6,122</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:OperatingIncomeLoss" id="Fact_e656146c3d254200b1d7c79c8135fb39" contextRef="c20221001to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">208,019</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%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_64bf3d68a9a94552bd3463e1e35b0df2" contextRef="c20231001to20231231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">9,263</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:NetIncomeLoss" id="Fact_af25cdfae24542caac610d75303df0eb" contextRef="c20221001to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">52,430</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;">Basic net 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="c20231001to20231231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.06</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="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>

  </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 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="c20231001to20231231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.06</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="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>

  </tr>


</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
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    <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 higher in the three months ended December 31, 2023
            compared to the same period in 2022 primarily due to the $<ix:nonFraction name="us-gaap:Revenues" id="Fact_75e24768ba824a2b9a04b8c91d513855" contextRef="c20231001to20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">50</ix:nonFraction> million milestone payment we earned from AstraZeneca when the FDA approved
            WAINUA for ATTRv-PN in the U.S., $<ix:nonFraction name="us-gaap:Revenues" id="Fact_14c3c8ccfb6f458f890a035fb5e35122" contextRef="c20231001to20231231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">36</ix:nonFraction> million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth
            quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbe30145442f43ab91936a9d68a84c1e7" continuedAt="Text_bbe30145442f43ab91936a9d68a84c1e8"><ix:continuation id="Text_23514d9c4d514db48477cf58c1cbf9f65" continuedAt="Text_23514d9c4d514db48477cf58c1cbf9f66">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbe30145442f43ab91936a9d68a84c1e8" continuedAt="Text_bbe30145442f43ab91936a9d68a84c1e9"><ix:continuation id="Text_23514d9c4d514db48477cf58c1cbf9f66" continuedAt="Text_23514d9c4d514db48477cf58c1cbf9f67">
<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 lower in the three months ended December 31,
            2023 compared to the same period in 2022 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_bbe30145442f43ab91936a9d68a84c1e9" continuedAt="Text_bbe30145442f43ab91936a9d68a84c1e10"><ix:continuation id="Text_23514d9c4d514db48477cf58c1cbf9f67" continuedAt="Text_23514d9c4d514db48477cf58c1cbf9f68">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbe30145442f43ab91936a9d68a84c1e10" continuedAt="Text_bbe30145442f43ab91936a9d68a84c1e11"><ix:continuation id="Text_23514d9c4d514db48477cf58c1cbf9f68" continuedAt="Text_23514d9c4d514db48477cf58c1cbf9f69">
<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: 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_bbe30145442f43ab91936a9d68a84c1e11" continuedAt="Text_bbe30145442f43ab91936a9d68a84c1e12"><ix:continuation id="Text_23514d9c4d514db48477cf58c1cbf9f69" continuedAt="Text_23514d9c4d514db48477cf58c1cbf9f610">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbe30145442f43ab91936a9d68a84c1e12" continuedAt="Text_bbe30145442f43ab91936a9d68a84c1e13"><ix:continuation id="Text_23514d9c4d514db48477cf58c1cbf9f610" continuedAt="Text_23514d9c4d514db48477cf58c1cbf9f611">
<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 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>

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</table>
</ix:continuation></ix:continuation>
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<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbe30145442f43ab91936a9d68a84c1e14" continuedAt="Text_bbe30145442f43ab91936a9d68a84c1e15"><ix:continuation id="Text_23514d9c4d514db48477cf58c1cbf9f612" continuedAt="Text_23514d9c4d514db48477cf58c1cbf9f613">
<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 loss per share by dividing the total net 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_bbe30145442f43ab91936a9d68a84c1e15" continuedAt="Text_bbe30145442f43ab91936a9d68a84c1e16"><ix:continuation id="Text_23514d9c4d514db48477cf58c1cbf9f613" continuedAt="Text_23514d9c4d514db48477cf58c1cbf9f614">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbe30145442f43ab91936a9d68a84c1e16"><ix:continuation id="Text_23514d9c4d514db48477cf58c1cbf9f614">
<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 incurred a net loss for the fourth quarter of 2023 and 2022. As a
            result, 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.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation></div>


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<DOCUMENT>
<TYPE>EX-10.3
<SEQUENCE>2
<FILENAME>exhibit10-3.htm
<DESCRIPTION>EXHIBIT 10.3
<TEXT>
<html>
  <head>
    <title></title>
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<body style="font-family: 'Times New Roman'; font-size: 10pt; text-align: left; color: #000000;" bgcolor="#ffffff">
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    <div>
      <div style="text-align: right; font-weight: bold;">Exhibit 10.3</div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;"><u>INDEMNITY AGREEMENT</u></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">THIS INDEMNITY AGREEMENT (the &#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;) is made and entered into this <font style="font-weight: bold;">[DAY] day of [MONTH], [YEAR]</font>
        by and between Ionis Pharmaceuticals, Inc., a Delaware corporation (the &#8220;<font style="font-weight: bold; font-style: italic;">Company</font>&#8221;), and <font style="font-weight: bold;">[DIRECTOR/OFFICER NAME] </font>(&#8220;<font style="font-weight: bold; font-style: italic;">Agent</font>&#8221;).</div>
      <div><br>
      </div>
      <div style="text-align: center;"><u>RECITALS</u></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-variant: small-caps;">WHEREAS</font><font style="font-size: 10pt;">, Agent performs a valuable service to the Company in [his/her] capacity as [<font style="font-weight: bold;">TITLE</font>];</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-variant: small-caps;">WHEREAS</font><font style="font-size: 10pt;">, the stockholders of the Company have adopted bylaws (the &#8220;<font style="font-weight: bold; font-style: italic;">Bylaws</font>&#8221;) providing for the indemnification of the directors, officers, employees and other agents of the Company, including persons serving at the request of the Company in such capacities
          with other corporations or enterprises, as authorized by the Delaware General Corporation Law, as amended (&#8220;<font style="font-weight: bold; font-style: italic;">Delaware Law</font>&#8221;);</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-variant: small-caps;">WHEREAS</font><font style="font-size: 10pt;">, the Bylaws and Delaware Law by their non-exclusive nature, permit contracts
          between the Company and its agents, officers, employees and other agents with respect to indemnification of such persons; and</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-variant: small-caps;">WHEREAS</font><font style="font-size: 10pt;">, in order to induce Agent to continue to serve as [<font style="font-weight: bold;">TITLE</font>], the Company has determined and agreed to enter into this Agreement with Agent;</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-variant: small-caps;">NOW, THEREFORE</font><font style="font-size: 10pt;">, in consideration of Agent's continued service [<font style="font-weight: bold;">TITLE</font>], after the date hereof, the parties hereto agree as follows:</font></div>
      <div><br>
      </div>
      <div style="text-align: center;"><u>AGREEMENT</u></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Services to the Company.&#160; Agent will serve, at the will of the Company or under separate contract, if any such contract exists, as [<font style="font-weight: bold;">TITLE</font>] or as
        a director, officer or other fiduciary of an affiliate of the Company (including any employee benefit plan of the Company) faithfully and to the best of [his/her] ability so long as she<font style="font-weight: bold;">&#160;</font>is duly elected and
        qualified in accordance with the provisions of the Bylaws or other applicable charter documents of the Company or such affiliate; provided, however, that Agent may at any time and for any reason resign from such position (subject to any contractual
        obligation that Agent may have assumed apart from this Agreement) and that the Company or any affiliate shall have no obligation under this Agreement to continue Agent in any such position.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">2.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Indemnity of Agent</u>.&#160; The Company hereby agrees to hold harmless and indemnify Agent to the fullest extent authorized or permitted by the provisions of the Bylaws and Delaware
        Law, as the same may be amended from time to time (but, only to the extent that such amendment permits the Company to provide broader indemnification rights than the Bylaws or Delaware Law permitted prior to adoption of such amendment).</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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              <div style="text-align: center; font-size: 8pt;">Page <font class="BRPFPageNumber">1</font> of 7</div>
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      </div>
      <div style="text-align: justify; text-indent: 36pt;">3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; <u>Additional Indemnity</u>.&#160; In addition to and not in limitation of the indemnification otherwise provided for herein, and subject only to the exclusions set forth in Section 4
        hereof, the Company hereby further agrees to hold harmless and indemnify Agent:</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160; against any and all expenses (including attorneys&#8217; fees), witness fees, damages, judgments, fines and amounts paid in settlement and any other amounts that Agent becomes legally
        obligated to pay because of any claim or claims made against or by her in connection with any threatened, pending or completed action, suit or proceeding, whether civil, criminal, arbitrational, administrative or investigative (including an action
        by or in the right of the Company) to which Agent is, was or at any time becomes a party, or is threatened to be made a party, because of the fact that Agent is, was or at any time becomes a director, officer, employee or other agent of Company, or
        is or was serving or at any time serves at the request of the Company as a director, officer, employee or other agent of another corporation, partnership, joint venture, trust, employee benefit plan or other enterprise; and</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; otherwise to the fullest extent as may be provided to Agent by the Company under the non-exclusivity provisions of Delaware Law and Section 42 of the Bylaws.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">4.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u></u><u>Limitations on Additional Indemnity</u>.&#160; No indemnity pursuant to Section 3 hereof shall be paid by the Company:</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; on account of any claim against Agent for an accounting of profits made from the purchase or sale by Agent of securities of the Company pursuant to the provisions of Section 16(b) of
        the Securities Exchange Act of 1934 and amendments thereto or similar provisions of any federal, state or local statutory law;</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;on account of Agent's conduct that was knowingly fraudulent or deliberately dishonest or that constituted willful misconduct;</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; on account of Agent's conduct that constituted a breach of Agent's duty of loyalty to the Company or resulted in any personal profit or advantage to which Agent was not legally
        entitled;</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; for which payment is actually made to Agent under a valid and collectible insurance policy or under a valid and enforceable indemnity clause, bylaw or agreement, except in respect of
        any excess beyond payment under such insurance, clause, bylaw or agreement;</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; if indemnification is not lawful (and, in this respect, both the Company and Agent have been advised that the Securities and Exchange Commission believes that indemnification for
        liabilities arising under the federal securities laws is against public policy and is, therefore, unenforceable and that claims for indemnification should be submitted to appropriate courts for adjudication); or</div>
      <div><br>
      </div>
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      </div>
      <div style="text-align: justify; text-indent: 72pt;">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; in connection with any proceeding (or part thereof) initiated by Agent, or any proceeding by Agent against the Company or its directors, officers, employees or other agents, unless (i)
        such indemnification is expressly required to be made by law, (ii) the proceeding was authorized by the Board of Directors of the Company, (iii) such indemnification is provided by the Company, in its sole discretion, pursuant to the powers vested
        in the Company under Delaware Law, or (iv) the proceeding is initiated pursuant to Section 9 hereof.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">5.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Continuation of Indemnity</u>.&#160; All agreements and obligations of the Company contained herein shall continue during the period Agent is a director, officer, employee or other
        agent of the Company (or is or was serving at the request of the Company as a director, officer, employee or other agent of another corporation, partnership, joint venture, trust, employee benefit plan or other enterprise) and shall continue
        thereafter so long as Agent shall be subject to any possible claim or threatened, pending or completed action, suit or proceeding, whether civil, criminal, arbitrational, administrative or investigative, by reason of the fact that Agent was serving
        in the capacity referred to herein.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">6.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Partial Indemnification</u>.&#160; Agent shall be entitled under this Agreement to indemnification by the Company for a portion of the expenses (including attorneys' fees), witness fees,
        damages, judgments, fines and amounts paid in settlement and any other amounts that Agent becomes legally obligated to pay in connection with any action, suit or proceeding referred to in Section 3 hereof even if not entitled hereunder to
        indemnification for the total amount thereof, and the Company shall indemnify Agent for the portion thereof to which Agent is entitled.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">7.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Notification and Defense of Claim</u>.&#160; Not later than thirty (30) days after receipt by Agent of notice of the commencement of any action, suit or proceeding, Agent will, if a
        claim in respect thereof is to be made against the Company under this Agreement, notify the Company of the commencement thereof; but the omission so to notify the Company will not relieve it from any liability which it may have to Agent otherwise
        than under this Agreement.&#160; With respect to any such action, suit or proceeding as to which Agent notifies the Company of the commencement thereof:</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;the Company will be entitled to participate therein at its own expense;</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; except as otherwise provided below, the Company may, at its option and jointly with any other indemnifying party similarly notified and electing to assume such defense, assume the
        defense thereof, with counsel reasonably satisfactory to Agent.&#160; After notice from the Company to Agent of its election to assume the defense thereof, the Company will not be liable to Agent under this Agreement for any legal or other expenses
        subsequently incurred by Agent in connection with the defense thereof except for reasonable costs of investigation or otherwise as provided below.&#160; Agent shall have the right to employ separate counsel in such action, suit or proceeding but the
        fees and expenses of such counsel incurred after notice from the Company of its assumption of the defense thereof shall be at the expense of Agent unless (i) the employment of counsel by Agent has been authorized by the Company, (ii) Agent shall
        have reasonably concluded that there may be a conflict of interest between the Company and Agent in the conduct of the defense of such action or (iii) the Company shall not in fact have employed counsel to assume the defense of such action, in each
        of which case the fees and expenses of Agent&#8217;s separate counsel shall be at the expense of the Company.&#160; The Company shall not be entitled to assume the defense of any action, suit or proceeding brought by or on behalf of the Company or as to which
        Agent shall have made the conclusion provided for in clause (ii) above; and</div>
      <div><br>
      </div>
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        <div class="BRPFPageBreak" style="page-break-after: always;">
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        <div style="width: 100%;" class="BRPFPageHeader"></div>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; the Company shall not be liable to indemnify Agent under this Agreement for any amounts paid in settlement of any action or claim effected without the Company&#8217;s written consent, which
        shall not be unreasonably withheld.&#160; The Company shall be permitted to settle any action except that it shall not settle any action or claim in any manner which would impose any penalty or limitation on Agent without Agent's written consent, which
        may be given or withheld in Agent's sole discretion.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">8.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Expenses</u>.&#160; The Company shall advance, prior to the final disposition of any proceeding, promptly following request therefor, all expenses incurred by Agent in connection with
        such proceeding upon receipt of an undertaking by or on behalf of Agent to repay said amounts if it shall be determined ultimately that Agent is not entitled to be indemnified under the provisions of this Agreement, the Bylaws, Delaware Law or
        otherwise.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">9.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; <u>Enforcement</u>.&#160; Any right to indemnification or advances granted by this Agreement to Agent shall be enforceable by or on behalf of Agent in any court of competent jurisdiction
        if (i) the claim for indemnification or advances is denied, in whole or in part, or (ii) no disposition of such claim is made within ninety (90) days of request therefor.&#160; Agent, in such enforcement action, if successful in whole or in part, shall
        also be entitled to be paid the expense of prosecuting her claim.&#160; It shall be a defense to any action for which a claim for indemnification is made under Section 7 hereof (other than an action brought to enforce a claim for expenses pursuant to
        Section 8 hereof, provided that the required undertaking has been tendered to the Company) that Agent is not entitled to indemnification because of the limitations set forth in Section 4 hereof.&#160; Neither the failure of the Company (including its
        Board of Directors or its stockholders) to have made a determination prior to the commencement of such enforcement action that indemnification of Agent is proper in the circumstances, nor an actual determination by the Company (including its Board
        of Directors or its stockholders) that such indemnification is improper shall be a defense to the action or create a presumption that Agent is not entitled to indemnification under this Agreement or otherwise.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">10.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Subrogation</u>.&#160; In the event of payment under this Agreement, the Company shall be subrogated to the extent of such payment to all of the rights of recovery of Agent, who shall
        execute all documents required and shall do all acts that may be necessary to secure such rights and to enable the Company effectively to bring suit to enforce such rights.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">11.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Non-Exclusivity of Rights</u>.&#160; The rights conferred on Agent by this Agreement shall not be exclusive of any other right which Agent may have or hereafter acquire under any
        statute, provision of the Company's Certificate of Incorporation or Bylaws, agreement, vote of stockholders or directors, or otherwise, both as to action in her official capacity and as to action in another capacity while holding office.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">12.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u></u><u>Survival of Rights</u>.</div>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="width: 100%;" class="BRPFPageFooter">
          <div>
            <div>
              <div style="text-align: center; font-size: 8pt;">Page <font class="BRPFPageNumber">4</font> of 7</div>
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        </div>
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        <div style="width: 100%;" class="BRPFPageHeader"></div>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The rights conferred on Agent by this Agreement shall continue after Agent has ceased to be a director, officer, employee or other agent of the Company or to serve at the request of
        the Company as a director, officer, employee or other agent of another corporation, partnership, joint venture, trust, employee benefit plan or other enterprise and shall inure to the benefit of Agent's heirs, executors and administrators.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; The Company shall require any successor (whether direct or indirect, by purchase, merger, consolidation or otherwise) to all or substantially all of the business or assets of the
        Company, expressly to assume and agree to perform this Agreement in the same manner and to the same extent that the Company would be required to perform if no such succession had taken place.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">13.&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Separability</u>.&#160; Each of the provisions of this Agreement is a separate and distinct agreement and independent of the others, so that if any provision hereof shall be held to be
        invalid for any reason, such invalidity or unenforceability shall not affect the validity or enforceability of the other provisions hereof.&#160; Furthermore, if this Agreement shall be invalidated in its entirety on any ground, then the Company shall
        nevertheless indemnify Agent to the fullest extent provided by the Bylaws, Delaware Law or any other applicable law.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">14.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Governing Law</u>.&#160; This Agreement shall be interpreted and enforced in accordance with the laws of the State of Delaware.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">15.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Amendment and Termination</u>.&#160; No amendment, modification, termination or cancellation of this Agreement shall be effective unless in writing signed by both parties hereto.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">16.&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;<u></u><u>Identical Counterparts</u>.&#160; This Agreement may be executed in one or more counterparts, each of which shall for all purposes be deemed to be an original but all of which
        together shall constitute but one and the same Agreement.&#160; Only one such counterpart need be produced to evidence the existence of this Agreement.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">17.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Headings</u>.&#160; The headings of the sections of this Agreement are inserted for convenience only and shall not be deemed to constitute part of this Agreement or to affect the
        construction hereof.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">18.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Notices</u>.&#160; All notices, requests, demands and other communications hereunder shall be in writing and shall be deemed to have been duly given (i) upon delivery if delivered by
        hand to the party to whom such communication was directed or (ii) upon the third business day after the date on which such communication was mailed if mailed by certified or registered mail with postage prepaid:</div>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="width: 100%;" class="BRPFPageFooter">
          <div>
            <div>
              <div style="text-align: center; font-size: 8pt;">Page <font class="BRPFPageNumber">5</font> of 7</div>
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          </div>
        </div>
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        <div style="width: 100%;" class="BRPFPageHeader"></div>
      </div>
      <div style="text-indent: 72pt;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If to Agent, at the address indicated on the signature page hereof.</div>
      <div><br>
      </div>
      <div style="text-indent: 72pt;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If to the Company, to</div>
      <div style="margin-left: 144pt;">Ionis Pharmaceuticals, Inc.</div>
      <div style="margin-left: 144pt;">2855 Gazelle Court</div>
      <div style="margin-left: 144pt;">Carlsbad, CA 92010</div>
      <div style="margin-left: 144pt;">Attention:&#160; General Counsel</div>
      <div style="margin-left: 144pt;">legalnotices@ionisph.com</div>
      <div><br>
      </div>
      <div style="text-align: justify;">or to such other address as may have been furnished to Agent by the Company.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-variant: small-caps;">IN WITNESS WHEREOF</font><font style="font-size: 10pt;">, the parties hereto have executed this Agreement on and as of the
          day and year first above written.</font></div>
      <div><br>
      </div>
      <table id="z6cab1c5d2605467c93089b3ff785811a" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" border="0" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 50%; vertical-align: top;"><br>
            </td>
            <td style="vertical-align: top;" colspan="2">
              <div>IONIS PHARMACEUTICALS, INC.</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;" rowspan="1"><br>
            </td>
            <td style="vertical-align: top;" colspan="2" rowspan="1"><br>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;"><br>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div>By:</div>
            </td>
            <td style="width: 45%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);"><br>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;"><br>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div>Name:</div>
            </td>
            <td style="width: 45%; vertical-align: top;">
              <div>Brett Monia</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;"><br>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div>Title:</div>
            </td>
            <td style="width: 45%; vertical-align: top;">
              <div>Chief Executive Officer</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table id="z6fce4df23aa4435ab463ee96237e7ae4" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" border="0" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 50%; vertical-align: top;"><br>
            </td>
            <td style="vertical-align: top;" colspan="2">
              <div>AGENT</div>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
            <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;"><br>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div>By:</div>
            </td>
            <td style="width: 45%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);"><br>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;"><br>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div>Name:</div>
            </td>
            <td style="width: 45%; vertical-align: top;"><br>
            </td>
          </tr>
          <tr>
            <td style="width: 50%; vertical-align: top;"><br>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div>Address:</div>
            </td>
            <td style="width: 45%; vertical-align: top;"><br>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="width: 100%;" class="BRPFPageFooter">
          <div>
            <div>
              <div style="text-align: center; font-size: 8pt;">Page <font class="BRPFPageNumber">6</font> of 7</div>
            </div>
          </div>
        </div>
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        <div style="width: 100%;" class="BRPFPageHeader"></div>
      </div>
      <div style="text-align: center; color: rgb(0, 0, 0); font-weight: bold;">Schedule of Directors and Executive Officers</div>
      <div style="text-align: center; color: rgb(0, 0, 0); font-weight: bold;">with Indemnity Agreements</div>
      <div><br>
      </div>
      <div>Joseph T. Baroldi, M.A., M.B.A., M.S., Executive Vice President, Chief Business Officer</div>
      <div>C. Frank Bennett, Ph.D., Executive Vice President, Chief Scientific Officer</div>
      <div>Spencer R. Berthelsen, M.D., Director</div>
      <div>Brian Birchler, Executive Vice President, Corporate and Development Operations</div>
      <div>Onaiza Cadoret-Manier, Executive Vice President, Chief Global Product Strategy and Operations Officer</div>
      <div>Allene M. Diaz, Director</div>
      <div>Richard S. Geary, Ph.D., Executive Vice President, Chief Development Officer</div>
      <div>Michael Hayden, C.M., O.B.C., M.B., Ch.B., Ph.D., F.R.C.P.(C), F.R.S.C., Director</div>
      <div>Joan E. Herman, Director</div>
      <div>Elizabeth L. Hougen, Executive Vice President and Chief Financial Officer</div>
      <div>Joseph Klein, III, Director</div>
      <div>Joseph Loscalzo, M.D., Ph.D., Chairman of the Board</div>
      <div>Brett P. Monia, Ph.D., Chief Executive Officer, Director</div>
      <div>Patrick R. O&#8217;Neil, Esq., Chief Legal Officer and General Counsel</div>
      <div>B. Lynne Parshall, Esq., Director</div>
      <div>Eugene Schneider, M.D., Executive Vice President, Chief Clinical Development and Operations Officer</div>
      <div>Eric E. Swayze, Ph.D., Executive Vice President, Research</div>
      <div>Joseph H. Wender, Director</div>
      <div>Michael Yang, Director</div>
      <div><br>
      </div>
      <div><br>
      </div>
      <div>
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          <div>
            <div>
              <div style="text-align: center; font-size: 8pt;">Page <font class="BRPFPageNumber">7</font> of 7</div>
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        </div>
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</DOCUMENT>
<DOCUMENT>
<TYPE>EX-10.25
<SEQUENCE>3
<FILENAME>exhibit10-25.htm
<DESCRIPTION>EXHIBIT 10.25
<TEXT>
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  <head>
    <title></title>
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    <div style="text-align: right; font-weight: bold;">Exhibit 10.25</div>
    <div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;"><u>FIRST AMENDMENT TO AMENDED AND RESTATED LEASE</u></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">THIS FIRST AMENDMENT TO AMENDED AND RESTATED LEASE </font><font style="font-size: 10pt;">(this &#8220;<font style="font-weight: bold;">Amendment</font>&#8221;)

          is entered into as of November 6, 2023, by and between <font style="font-weight: bold;">LOTS 21 &amp; 22 OWNER (DE) LLC</font>, a Delaware limited liability company<font style="font-weight: bold;">&#160;</font>(&#8220;<font style="font-weight: bold;">Landlord</font>&#8221;),

          and <font style="font-weight: bold;">IONIS PHARMACEUTICALS, INC.</font>, a Delaware corporation (&#8220;<font style="font-weight: bold;">Tenant</font>&#8221;).</font></div>
      <div>&#160;</div>
      <div style="text-align: center; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>R E C I T A L S</u></font><font style="font-size: 10pt;">:</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt;">A.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Landlord and Tenant are parties to that certain Amended and Restated Lease Agreement dated as of August 21, 2023 (the &#8220;<font style="font-weight: bold;">Lease</font>&#8221;) for certain
        premises consisting of approximately 164,757 gross square feet, all located within Lots 21 &amp; 22, Whiptail Loop W in Carlsbad, California 92010 (the &#8220;<font style="font-weight: bold;">Premises</font>&#8221;).</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 36pt;">B.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;In connection therewith, Landlord and Tenant desire to amend the Lease as set forth below.</div>
      <div>&#160;</div>
      <div style="text-align: center; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;"><u>A G R E E M E N T</u></font><font style="font-size: 10pt;">:</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">NOW, THEREFORE</font><font style="font-size: 10pt;">, in consideration of the mutual covenants contained herein and for other good
          and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, Landlord and Tenant agree to amend the Lease as follows:</font></div>
      <font style="font-size: 10pt;"> </font>
      <div style="font-size: 10pt;">&#160;</div>

      <div style="text-align: justify; margin-bottom: 12pt; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;">1.</font><font class="TRGRRTFtoHTMLTab" style="display: inline-block; font-size: 10pt; width: 36pt;">&#160;</font><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;"><u>Work Letter</u></font>.&#160; Schedule 9 to Exhibit B
          of the Lease titled &#8220;LCW by Tenant and TI by Landlord&#8221; regarding the Landlord&#8217;s Construction Work by Tenant and the Tenant Improvements by Landlord is hereby deleted in its entirety and replaced with the revised Schedule 9 titled &#8220;LCW by Tenant
          and TI by Landlord&#8221; attached hereto as <font style="font-family: 'Times New Roman',Times,serif;"><u>Exhibit 1</u></font>.</font></div>
      <div style="text-align: justify; margin-bottom: 12pt; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;">2.</font><font class="TRGRRTFtoHTMLTab" style="display: inline-block; font-size: 10pt; width: 36pt;">&#160;</font><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;"><u>Miscellaneous</u></font>.&#160; Except as modified
          herein, the Lease and all of the terms and provisions thereof shall remain unmodified and in full force and effect as originally written.&#160; In the event of any conflict or inconsistency between the provisions of the Lease and the provisions of
          this Amendment, the provisions of this Amendment shall control.&#160; All terms used herein but not defined herein which are defined in the Lease shall have the same meaning for purposes hereof as they do for purposes of the Lease.&#160; The Recitals set
          forth above in this Amendment are hereby incorporated by this reference.&#160; This Amendment shall be binding upon and shall inure to the benefit of the parties hereto and their respective beneficiaries, successors and assigns. It is understood and
          acknowledged that there are no oral agreements between the parties hereto affecting the matters set forth in this Amendment and this Amendment constitutes the parties&#8217; entire agreement with respect to the matters set forth in this Amendment and
          supersedes and cancels any and all previous negotiations, arrangements, agreements and understandings, if any, between the parties hereto or with respect to the subject matter thereof, and none thereof shall be used to interpret or construe this
          Amendment.</font></div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;">3.</font><font class="TRGRRTFtoHTMLTab" style="display: inline-block; font-size: 10pt; width: 36pt;">&#160;</font><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;"><u>Counterparts</u></font>.&#160; This Amendment may be executed in any number of
          original or electronic counterparts which shall be treated as originals for all purposes, and by each of the undersigned on separate counterparts, which counterparts taken together shall constitute one and the same instrument.</font></div>
      <div>&#160;</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="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: justify; text-indent: 36pt; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">IN WITNESS WHEREOF</font><font style="font-size: 10pt;">, the undersigned have executed this Amendment as of the day and year
          first above written.</font></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: rgb(0, 0, 0);" id="z5f26ad9dcc494fa689da3fd62964aba6">

          <tr>
            <td colspan="2" style="vertical-align: top;">
              <div style="text-align: justify; font-size: 12pt;"><font style="font-size: 10pt; font-weight: bold;">LANDLORD</font><font style="font-size: 10pt;">:</font></div>
            </td>
            <td style="width: 65%; vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 5%; vertical-align: top;">&#160;</td>
            <td style="width: 30%; vertical-align: top;">&#160;</td>
            <td style="width: 65%; vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td colspan="2" style="vertical-align: top;">
              <div style="text-align: justify; font-weight: bold;">LOTS 21 &amp; 22 OWNER (DE) LLC,</div>
            </td>
            <td style="width: 65%; vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td colspan="2" style="vertical-align: top;">
              <div style="text-align: justify;">a Delaware limited liability company</div>
            </td>
            <td style="width: 65%; vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 5%; vertical-align: top;">&#160;</td>
            <td style="width: 30%; vertical-align: top;">&#160;</td>
            <td style="width: 65%; vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 5%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify;">By:</div>
            </td>
            <td style="width: 30%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify; font-size: 12pt;"><font style="font-size: 10pt; font-style: italic;">/s/ Tycho Suter</font></div>
            </td>
            <td style="width: 65%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 5%; vertical-align: top; padding-bottom: 2px;">
              <div style="text-align: justify;">Name:</div>
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            <td style="width: 30%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">
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<DOCUMENT>
<TYPE>EX-10.80
<SEQUENCE>4
<FILENAME>exhibit10-80.htm
<DESCRIPTION>EXHIBIT 10.80
<TEXT>
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      <div style="font-style: normal; font-weight: bold;">Exhibit 10.80</div>
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        Execution Version</div>
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    <div style="color: rgb(0, 0, 0);">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>
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            <div>ARTICLE 1 OVERVIEW</div>
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            <div style="text-align: right;">1</div>
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          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
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            <div style="text-align: right;">1</div>
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            <div>License Grants to Otsuka</div>
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            <div>2.3</div>
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            <div>Sublicensing and Subcontracting Terms</div>
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            <div>2.7</div>
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            <div>4.1</div>
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            <div>Development Diligence Obligations</div>
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            <div>4.3</div>
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            <div>Otsuka Territory-Specific Development Plan</div>
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            <div>Data Transfer</div>
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            <div style="text-align: right;">13</div>
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            <div>Regulatory Responsible Party</div>
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          <td style="width: 8%; vertical-align: top; text-align: right;">13</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>5.2</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Regulatory Subcommittee</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">14</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>5.3</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Correspondences with Regulatory Authorities</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">14</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>5.4</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Regulatory Meetings</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">14</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>5.5</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Regulatory Submissions</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">14</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>5.6</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Cooperation</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">15</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>5.7</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Cost of Regulatory Activities</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">15</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>5.8</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>No Harmful Actions</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">15</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">i</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
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    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>5.9</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Right of Reference</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">15</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>5.10</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Pharmacovigilance; Safety Information</div>
          </td>
          <td style="width: 8%; vertical-align: top; text-align: right;">16</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>5.11</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Pharmacovigilance Subcommittee</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">16</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>5.12</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Ionis Internal Oligonucleotide Safety Database</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">16</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>5.13</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Recall, Withdrawal, or Field Alerts</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">17</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 8%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="3">
            <div>ARTICLE 6 COMMERCIALIZATION AND MEDICAL AFFAIRS</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">18</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>6.1</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Commercialization Responsibilities for Licensed Product</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">18</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>6.2</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Commercialization and Medical Affairs Reporting</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">18</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>6.3</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Pricing</div>
          </td>
          <td style="width: 8%; vertical-align: top; text-align: right;">19</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>6.4</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Global Brand Strategic and Operating Plan</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">19</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>6.5</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Otsuka Territory Brand Strategic and Operating Plan</div>
          </td>
          <td style="width: 8%; vertical-align: top; text-align: right;">19</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>6.6</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Otsuka Commercialization Diligence Obligations</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">19</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>6.7</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Medical Affairs Plans.</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">19</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>6.8</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Standards of Conduct; Compliance</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">20</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>6.9</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Product Materials</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">20</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>6.10</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Diversion</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">20</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 8%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="3">
            <div>ARTICLE 7 MANUFACTURING</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">21</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>7.1</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Responsibility</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">21</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>7.2</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Supply and Quality Agreements; Manufacturing Costs</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">22</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>7.3</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Audits and Inspections</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">23</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>7.4</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Manufacturing Technology Transfer</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">23</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 8%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="3">
            <div>ARTICLE 8 GOVERNANCE</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">24</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>8.1</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Joint Steering Committee</div>
          </td>
          <td style="width: 8%; vertical-align: top; text-align: right;">24</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>8.2</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Additional Committees</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">26</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>8.3</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Additional Participants</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">27</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>8.4</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Decision-Making</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">27</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>8.5</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Resolution of Committee Disputes</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">27</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>8.6</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Day-to-Day Responsibilities</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">28</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>8.7</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Alliance Managers</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">28</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3">
            <div>ARTICLE 9 PAYMENTS</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">29</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>9.1</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Upfront Payment</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">29</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>9.2</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Milestone Payments</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">29</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>9.3</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Royalties</div>
          </td>
          <td style="width: 8%; 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;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>9.4</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Other Amounts Payable</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">32</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>9.5</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Financial Records and Audits</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">33</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">ii</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
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    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>9.6</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>No Refunds</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">33</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>9.7</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Accounting Standards</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">33</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>9.8</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Method of Payment; Exchange Rate</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">33</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>9.9</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Blocked Payments</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">33</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>9.10</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Taxes</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">34</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>9.11</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Late Payments; Disputed Payments</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">34</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3">
            <div>ARTICLE 10 INTELLECTUAL PROPERTY</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">35</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>10.1</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Inventions</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">35</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>10.2</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Patent Prosecution</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">36</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>10.3</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Enforcement Against Third Party Infringement or Misappropriation</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">38</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>10.4</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Defense of Third-Party Patent Challenges</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">40</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>10.5</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Third Party Infringement Claims</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">41</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>10.6</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Patent Challenges of Third-Party Patent Rights</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">42</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>10.7</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Patent Term Extensions</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">43</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>10.8</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Unified Patent Court</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">43</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>10.9</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Common Interest</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">43</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>10.10</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Product Trademarks</div>
          </td>
          <td style="width: 8%; 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="3" rowspan="1">&#160;</td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3">
            <div>ARTICLE 11 REPRESENTATIONS, WARRANTIES, AND COVENANTS</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">47</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>11.1</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Mutual Representations and Warranties</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">47</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>11.2</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Additional Ionis Representations and Warranties</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">48</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>11.3</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Additional Otsuka Representations and Warranties</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">50</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>11.4</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Additional Covenants</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">50<br>
            </div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>11.5</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Disclaimer</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">51</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>11.6</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Limitation of Liability</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">51</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3">
            <div>ARTICLE 12 CONFIDENTIALITY</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">52</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>12.1</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Duty of Confidence</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">52</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>12.2</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Confidential Information</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">52</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>12.3</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exemptions</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">53</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>12.4</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Authorized Disclosures</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">53</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>12.5</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Publications</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">54</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>12.6</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Publicity; Use of Names</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">55</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>12.7</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Acknowledgement</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">56</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 8%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="3">
            <div>ARTICLE 13 INDEMNIFICATION</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">57</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>13.1</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Indemnification by Ionis</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">57</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>13.2</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Indemnification by Otsuka</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">57</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">iii</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>13.3</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Indemnification Procedure</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">57</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>13.4</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Insurance</div>
          </td>
          <td style="width: 8%; vertical-align: top; text-align: right;">58</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3">
            <div>ARTICLE 14 TERM AND TERMINATION</div>
          </td>
          <td style="width: 8%; vertical-align: top; text-align: right;">58</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>14.1</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Term</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">58</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>14.2</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Termination for Material Breach</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">58</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>14.3</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Termination by Otsuka for Convenience</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">58</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>14.4</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Discontinuation of Development and Commercialization</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">59</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>14.5</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Termination For Patent Challenge</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">59</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>14.6</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Termination for Insolvency</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">59</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>14.7</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Rights in Bankruptcy</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">60</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>14.8</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Full Force and Effect During Notice Period</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">60<br>
            </div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>14.9</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Effects of Termination</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">60</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>14.10</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Survival; Accrued Rights</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">65</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
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        <tr>
          <td style="vertical-align: top;" colspan="3">
            <div>ARTICLE 15 DISPUTE RESOLUTION; GOVERNING LAW</div>
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          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">65</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>15.1</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Executive Officers; Disputes</div>
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          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">65</div>
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        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>15.2</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Arbitration</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">65</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>15.3</div>
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          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Intellectual Property Disputes</div>
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          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">66</div>
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        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>15.4</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Equitable Remedies</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">67</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>15.5</div>
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          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Governing Law; English Language</div>
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          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">67</div>
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        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 8%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
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            <div>ARTICLE 16 MISCELLANEOUS</div>
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          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">67</div>
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        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
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            <div>16.1</div>
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            <div>Assignment</div>
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          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">67</div>
          </td>
        </tr>
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          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>16.2</div>
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          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Entire Agreement; Amendment</div>
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          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">67</div>
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        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>16.3</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>No Strict Construction; Interpretation</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">68</div>
          </td>
        </tr>
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          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>16.4</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Severability</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">69</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>16.5</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Force Majeure</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">69</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>16.6</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Notices</div>
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          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">69</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>16.7</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Further Assurances</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">70</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>16.8</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Performance by Affiliates</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">70</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>16.9</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Agency</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">70</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>16.10</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Binding Effect; No Third-Party Beneficiaries or Obligors</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">70</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>16.11</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>No Waiver</div>
          </td>
          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">70</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>16.12</div>
          </td>
          <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Cumulative Remedies</div>
          </td>
          <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">71</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div>16.13</div>
          </td>
          <td style="width: 80%; vertical-align: top;">
            <div>Counterparts</div>
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          <td style="width: 8%; vertical-align: top;">
            <div style="text-align: right;">71</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
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    <div style="text-align: center; font-weight: bold;">LICENSE AGREEMENT</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">This <font style="font-weight: bold; font-variant: small-caps;">License Agreement</font><font style="font-weight: bold;">&#160;</font>(this &#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;)
      is made and entered into as of December 15, 2023 (the &#8220;<font style="font-weight: bold; font-style: italic;">Effective Date</font>&#8221;) between <font style="font-weight: bold; font-variant: small-caps;">Ionis Pharmaceuticals, Inc.</font>, a Delaware
      corporation, having its principal place of business at 2855 Gazelle Court, Carlsbad CA 92010 USA (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;), and Otsuka Pharmaceutical Co., Ltd., a company organized and existing under the
      laws of Japan, having a place of business at 2-9, Kanda Tsukasa-machi, Chiyoda-ku, Tokyo 101-8535, Japan (&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka</font>&#8221;). Ionis and Otsuka may be referred to in this Agreement individually as a &#8220;<font style="font-weight: bold; font-style: italic;">Party</font>&#8221; and collectively as the &#8220;<font style="font-weight: bold; font-style: italic;">Parties</font>.&#8221; Capitalized terms used in this Agreement, whether used in the singular or the plural, have
      the meaning set forth in <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 1</u> (Definitions). All attached appendices and schedules are a part of this Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">RECITALS</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">WHEREAS</font>, Ionis possesses certain Patent Rights, Know-How, technology and expertise with respect to research, development, and manufacturing of drugs for the
      treatment of HAE, and has regulatory and commercial capabilities in the Ionis Territory;</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">WHEREAS</font>, Otsuka (itself and through its Affiliates) has expertise in the development and commercialization of biopharmaceutical products and has regulatory,
      development, and commercial capabilities in the Otsuka Territory; and</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">WHEREAS</font>, the Parties desire to collaborate to Develop and Commercialize the Licensed Products, and Ionis wishes to grant Otsuka and Otsuka wishes to receive an
      exclusive license to Develop and Commercialize the Licensed Products in the Otsuka Territory, in each case, as set forth in, and subject to the terms of, this Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">NOW THEREFORE</font>, the Parties agree as follows:</div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 1</div>
    <div style="text-align: center; font-weight: bold;">OVERVIEW</div>
    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Development and Commercialization</font>. As of the Effective Date, Ionis is Developing a Licensed Product in ongoing Clinical Trials in both the Otsuka Territory and the Ionis Territory (such studies, as
              further described and defined in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan)). Under this Agreement, the Parties intend (a) that Ionis will continue to conduct the Ongoing Cross-Territory Studies in accordance with the
              Cross-Territory Clinical Development Plan, at [***] and (b) to share the costs of all Future Cross-Territory Studies included in the Cross-Territory Clinical Development Plan as of the Effective Date and any additional Cross-Territory
              Clinical Studies included in any updated version of the Cross-Territory Clinical Development Plan approved by [***], in each case, in accordance with the [***]. In addition, the Parties intend for Ionis to Commercialize the Licensed Products
              in the Ionis Territory and Otsuka to Commercialize the Licensed Products in the Otsuka Territory, which Commercialization activities will be consistent with the global commercialization and global medical affairs strategy (as further
              described in <u>Article 6</u> (Commercialization and Medical Affairs)).</div>
          </td>
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    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Governance</font>. The Parties have agreed to form a joint steering committee to oversee and coordinate the Development, Manufacturing, and Commercialization activities with respect to the Licensed Products
              under this Agreement.</div>
          </td>
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    <div>&#160;</div>
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            <div><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>
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    <div>&#160;</div>
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    <div style="text-align: center; font-weight: bold;">ARTICLE 2</div>
    <div style="text-align: center; font-weight: bold;">LICENSES</div>
    <div>&#160;</div>
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            <div><font style="font-weight: bold;">License Grants to Otsuka</font>. Subject to the terms of this Agreement (including Ionis&#8217; retained rights set forth in <u>Section 2.5</u> (No Other Rights and Retained Rights; Negative Covenant)), Ionis
              hereby grants to Otsuka:</div>
          </td>
        </tr>

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    <div>&#160;</div>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>an exclusive, royalty-bearing license, with the right to grant sublicenses solely in accordance with <u>Section 2.3.1(a)</u> (Rights of Otsuka to Grant Sublicenses), under the Ionis Technology and the Unitary Product Trademark, in each
              case, to (a) Develop the Licensed Products in the Field in the Otsuka Territory in accordance with the Otsuka Territory-Specific Development Plan solely for Commercialization and for the conduct of Medical Affairs for such Licensed Products
              in the Field in the Otsuka Territory and (b) Commercialize and conduct Medical Affairs for the Licensed Products in the Field in the Otsuka Territory. For clarity, the license grant under this <u>Section 2.1.1</u> (License Grants to Otsuka)
              does not include the right to Manufacture the Licensed Products.</div>
          </td>
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    <div>&#160;</div>
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          <td style="width: 39.6pt; vertical-align: top;">2.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>a non-exclusive, royalty-bearing license, with the right to grant sublicenses solely in accordance with <u>Section 2.3.1(b)</u> (Rights of Otsuka to Grant Sublicenses), under the Ionis Technology and the Unitary Product Trademark solely
              to (a) Package and Label the Licensed Products in the Field in the Territory and (b) Manufacture the Licensed Products in the Field in the Territory from and after the time Otsuka provides a Manufacturing Handover Notice, in each case ((a)
              and (b)), solely for Commercialization and for the conduct of Medical Affairs for such Licensed Products in the Field in the Otsuka Territory.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">License Grant to Ionis</font>. Subject to the terms of this Agreement, including Otsuka&#8217;s retained rights set forth in <u>Section 2.5</u> (No Other Rights and Retained Rights; Negative Covenants), Otsuka
              hereby grants to Ionis an exclusive, royalty-free, fully-paid, perpetual license, with the right to grant sublicenses through multiple tiers, under the Otsuka Technology solely to (a) Develop the Licensed Products in the Ionis Territory and
              the Otsuka Territory; <font style="font-style: italic;">provided</font> that, unless this Agreement has been terminated, any such Development in the Otsuka Territory will be conducted solely in accordance with the Cross-Territory Clinical
              Development Plan and the Non-Clinical HAE Development Plan, (b) Manufacture the Licensed Products worldwide in accordance with this Agreement, and (c) Commercialize the Licensed Products in the Ionis Territory in accordance with this
              Agreement and, subject to <u>Section 14.9.5</u> (Sublicenses), worldwide following any termination of this Agreement.&#160; </div>
          </td>
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    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Sublicensing and Subcontracting Terms</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
          </td>
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            <div><font style="font-weight: bold;">Rights of Otsuka to Grant Sublicenses</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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            <div>Subject to the terms of this Agreement, Otsuka will have the right to grant sublicenses of the rights granted under <u>Section 2.1.1</u> (License Grants to Otsuka) (i) [***], and (ii) [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Subject to the terms of this Agreement, Otsuka will have the right to grant sublicenses of the rights granted under <u>Section 2.1.2</u> (License Grants to Otsuka) (i) [***], and (ii) [***].</div>
          </td>
        </tr>

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    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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    </div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Right to Subcontract</font>. Each Party may engage one or more Third Party subcontractors to perform services in furtherance of the performance of its obligations or exercise of its rights under this
              Agreement, including any Third Party contract manufacturer, contract research organization, contract sales organization, wholesaler or distributor (including a distributor that is engaged to conduct promotional activities with respect to the
              Licensed Products on such Party&#8217;s behalf and under such Party&#8217;s control) (&#8220;<font style="font-weight: bold; font-style: italic;">Subcontractors</font>&#8221;); <font style="font-style: italic;">provided </font>that (a) neither Party will engage
              any such Subcontractor that has been Debarred/Excluded; and (b) no engagement of any such Subcontractors will relieve the engaging Party of its obligations under this Agreement or any liability hereunder.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd21ad8b666ae4268a86b6bd3217a52c1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.3.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Sublicense and Subcontract Agreements</font>. Each agreement pursuant to which a sublicense is granted to a Sublicensee by Otsuka pursuant to this <u>Section 2.3</u> (Sublicensing and Subcontracting
              Terms), each agreement pursuant to which a sublicense is granted to a Sublicensee by Ionis of the rights granted to it under <u>Section 2.2</u> (License Grant to Ionis), and each agreement pursuant to which a Party engages any Subcontractor,
              in each case after the Effective Date and during the Term, will (a) be subject and subordinate to this Agreement, (b) be consistent with the terms of this Agreement, (c) include obligations of confidentiality and non-use applicable to the
              Confidential Information of the other Party that are at least as stringent as those set forth in <u>Article 12</u> (Confidentiality), and (d) include terms that are consistent with the intellectual property provisions set forth in this
              Agreement. As soon as reasonably practicable after execution of any sublicense agreement with a Sublicensee after the Effective Date, [***]. In addition, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.3.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Responsibility for Sublicensees and Subcontractors</font>. Notwithstanding any sublicense, the sublicensing or subcontracting Party will remain primarily liable to the other Party for the performance of all
              of its obligations under, and such Party&#8217;s compliance with all provisions of, this Agreement. Each Party agrees that it will be fully responsible and liable for any breach of the terms of this Agreement by any of its Sublicensees or
              Subcontractors to the same extent as if such Party itself has committed any such breach.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Collaboration Technology Enabling License</font>. Subject to the terms and conditions of this Agreement (and without limiting the licenses granted to Otsuka under <u>Section 2.1</u> (License Grants to
              Otsuka)), Otsuka hereby grants Ionis a fully-paid, royalty-free, irrevocable, worldwide, non-exclusive, sublicensable (through multiple tiers) license under any Otsuka Collaboration Know-How and Otsuka Collaboration Patent Rights (excluding
              any Product-Specific Patents) to Exploit products that include an oligonucleotide as an active pharmaceutical ingredient (other than a Licensed Product); <font style="font-style: italic;">provided</font> that Ionis may only grant a
              sublicense under the rights granted in this <u>Section 2.4</u> (Collaboration Technology Enabling License) if such sublicense includes the grant of a license under Know-How or Patent Rights Controlled by Ionis or its Affiliates to Exploit
              such products that include an oligonucleotide as an active pharmaceutical ingredient (other than a Licensed Product).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z1a9bed71b1374fc0812454a06c449b9c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Other Rights and Retained Rights; Negative Covenant</font>.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">3</font></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;" noshade="noshade"></div>
    </div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.5.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Other Rights and Retained Rights</font>. Nothing in this Agreement will be interpreted to grant a Party any rights under any intellectual property rights owned or Controlled by the other Party, including
              Ionis Technology or Otsuka Technology, in each case, that are not expressly granted herein, whether by implication, estoppel, or otherwise. Otsuka will not practice the Ionis Technology other than as expressly licensed and permitted under
              this Agreement and Ionis will not practice the Otsuka Technology other than as expressly licensed and permitted under this Agreement. Any rights not expressly granted to a Party by the other Party under this Agreement are hereby retained by
              such other Party. Without limiting the foregoing, (a) Ionis hereby expressly retains the right to perform (i) Development activities for the Licensed Products worldwide in accordance with the Cross-Territory Clinical Development Plan and the
              Non-Clinical HAE Development Plan, (ii) Manufacturing activities worldwide, and (iii) Ionis&#8217; other obligations under this Agreement, and (b) Otsuka hereby expressly retains the right to perform Development activities for the Licensed Products
              in the Field in the Otsuka Territory in accordance with the Otsuka Territory-Specific Development Plan solely for Commercialization and for the conduct of Medical Affairs for such Licensed Products in the Field in the Otsuka Territory and to
              Manufacture the Licensed Products in the Field in the Territory solely for Commercialization and for the conduct of Medical Affairs for such Licensed Products in the Field in the Otsuka Territory, in each case, in accordance with this
              Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zad41dd433f834a4b8c453c6fb2a4cfb4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.5.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Negative Covenant</font>. Ionis shall not, and shall cause its Affiliates to not, grant or convey any right to any Third Party (pursuant to a license grant, collaboration or services agreement, option
              grant, or otherwise) that would be in conflict with, limit the scope of, or otherwise adversely affect the licenses granted to Otsuka pursuant to <u>Section 2.1</u> (License Grants to Otsuka).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z2819eaba5b174f59871f1fddc99385ee" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Existing Third-Party IP Agreements</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5070738efb46416b8415968a13c91428" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.6.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Compliance</font>. Otsuka acknowledges and agrees that (a) the rights and licenses granted to Otsuka under this Agreement are subject to the applicable terms of all Existing Third-Party IP Agreements with
              respect to the Ionis Technology that is being sublicensed thereunder to Otsuka, (b) Ionis&#8217; ability to comply with its obligations, and grant rights and licenses to Otsuka, under this Agreement are limited by any and all requirements and
              restrictions imposed on Ionis under the Existing Third-Party IP Agreements with respect to the Ionis Technology that is being sublicensed to Otsuka by Ionis under such Existing Third-Party IP Agreements, and (c) Ionis will not be required to
              take any action or inaction pursuant to this Agreement that would cause Ionis to be in breach of any Existing Third-Party IP Agreement or to grant any rights to Otsuka hereunder that are in violation of, or inconsistent with, any Existing
              Third-Party IP Agreement. Otsuka will abide by the applicable terms of the Existing Third-Party IP Agreements, and, subject to [***], the applicable terms of any amendments, in each case, to the extent such terms are disclosed in the copies
              of the Existing Third-Party IP Agreements, and amendments thereto, that are provided or made available to Otsuka.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.6.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Existing Third-Party IP Amendments</font>. During the Term, Ionis will promptly furnish Otsuka with copies of any amendment to any Existing Third-Party IP Agreement to the extent related to any of the
              rights sublicensed to Otsuka hereunder, from which copies Ionis may redact confidential or commercially sensitive information or other information that is not relevant to the rights sublicensed to Otsuka pursuant to the applicable Existing
              Third-Party IP Agreement. During the Term, Ionis shall: (a) [***]; (b) [***]; (c) [***]; and (d) [***]. Notwithstanding any provision to the contrary in this Agreement, as between the Parties, [***] shall be solely responsible for the payment
              of all license fees, royalties, milestone payments, and other payment obligations under all Existing Third-Party IP Agreements.</div>
          </td>
        </tr>

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    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">New Third-Party IP Agreements</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.7.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Identification of New In-License Agreements</font>. If either Party intends to obtain Control of any Patent Rights or Know-How from a Third Party (whether by acquisition or license) that such Party believes
              are [***] to Exploit the Licensed Compound or a Licensed Product (other than in connection with a Change of Control of a Party or as a result of the acquisition by a Party of a Third Party by merger, acquisition, or similar transaction or
              series of related transactions) (such Patent Rights and Know-How, &#8220;<font style="font-weight: bold; font-style: italic;">Identified Rights</font>&#8221;), then such Party will notify the other Party of the Identified Rights.</div>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.7.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Potential In-Licenses</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 75.6pt;"><br>
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          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Acquisition of Potential In-Licenses</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z85611c1087ec4de6958be25be60164a6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

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          <td style="width: 18pt; vertical-align: top;">i.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***] that [***] in the Exploitation of a Licensed Product in [***] Territory, whether by license or acquisition, (each agreement to license or acquire such Identified Rights, a &#8220;<font style="font-weight: bold; font-style: italic;">Potential
                In-License</font>&#8221;) in accordance with this <u>Section 2.7.2</u> (Potential In-Licenses). If [***] after the Effective Date, then [***]&#160; will [***]. If [***] pursuant to this <u>Section 2.7.2(a)</u> (Acquisition of Potential In-Licenses),
              then [***] with respect to [***] to Exploit the Licensed Products. [***] such Potential In-License will [***]. [***]. If the Identified Rights to be licensed or acquired under a Potential In-License would constitute Ionis Core Technology or
              Ionis Manufacturing and Analytical Technology if such Identified Rights were Controlled by Ionis (any such Identified Rights, &#8220;<font style="font-weight: bold; font-style: italic;">Core or Manufacturing Identified Rights</font>&#8221;) then, [***]
              such Potential In-License (a &#8220;<font style="font-weight: bold; font-style: italic;">Core or Manufacturing Potential In-License</font>&#8221;) in accordance with <u>Section 2.7.2(c)i</u> (Non-Approved Potential In-Licenses).</div>
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    <div>&#160;</div>
    <table id="zb8feaa05f20d47daa559b43089548383" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

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          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If either Party [***] and if the Parties [***], then [***]. At either Party&#8217;s request if [***] in accordance with this <u>Section 2.7.2(a)ii</u> (Acquisition of Potential In-Licenses), the Parties will [***]. If the [***], then the
              Potential In-License [***] for all purposes of this Agreement. If [***], then Ionis will [***]. If Ionis [***] pursuant to this <u>Section 2.7.2(a)ii</u> (Acquisition of Potential In-Licenses) and Ionis [***] in accordance with this <u>Section
                2.7.2(a)ii</u> (Acquisition of Potential In-Licenses),<font style="font-weight: bold; font-style: italic;">&#160;</font>then [***]. If Ionis [***], then Otsuka will [***] in accordance with the terms of this <u>Section 2.7.2(a)ii</u>
              (Acquisition of Potential In-Licenses) and Otsuka will [***]. </div>
          </td>
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    </table>
    <div>&#160;</div>
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          <td style="width: 75.6pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Collaboration In-Licenses</font>. For any Potential In-License that [***] in accordance with <u>Section 2.7.2(a)</u> (Acquisition of Potential In-Licenses), and for [***] (i) such Potential In-License will
              [***], (ii) the Party [***] will [***], to the extent set forth in <u>Section 2.7.2(a)ii</u> (Acquisition of Potential In-Licenses), (iii) the Patent Rights or Know-How in-licensed under such [***], and (iv) (A) each Party will [***], and
              (B) the Parties will [***]. The Party that [***] will [***] pursuant to this <u>Section 2.7.2(b)</u> (Collaboration In-License), and such other Party will [***].</div>
          </td>
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    </table>
    <div>&#160;</div>
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            <div><font style="font-weight: bold;">[***] Potential In-Licenses</font>.</div>
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    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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          <td style="width: 111.6pt;"><br>
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            <div>If [***] a Potential In-License [***], then (A) such Potential In-License [***],<font style="background-color: rgb(0, 255, 255);">&#160;</font>(B) subject to <u>Section 2.7.2(c)ii</u> ([***] Potential In-Licenses), the Patent Rights and
              Know-How in-licensed under such Potential In-License [***], (C) except as set forth in clause (D) of this <u>Section 2.7.2(c)i</u> ([***] Potential In-Licenses), Ionis will [***] and, subject to <u>Section 2.7.2(c)ii</u> ([***] Potential
              In-Licenses), will [***]; <font style="font-style: italic;">provided</font> that if such Potential In-License [***], then [***], and Ionis [***] in accordance with <u>Section 2.7.2(c)ii</u> ([***] Potential In-Licenses), then Otsuka [***],
              and (D) if such Potential In-License (1) was [***] pursuant to <u>Section 2.7.2(a)</u> (Acquisition of Potential In-Licenses), (2) was not [***], and (3) is not [***], then [***] in accordance with this Agreement [***], and the terms of this
              <u>Section 2.7.2</u> (Potential In-Licenses) [***].<font style="font-weight: bold; font-style: italic;">&#160;</font>If Ionis [***] in accordance with <u>Section 2.7.2(a)</u> (Acquisition of Potential In-Licenses),<font style="font-weight: bold; font-style: italic;">&#160;</font>then Otsuka [***]. If [***], then Otsuka [***] in accordance with this <u>Section 2.7.2(c)i</u> ([***] Potential In-Licenses) and Otsuka will [***].</div>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 111.6pt;"><br>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If Ionis [***],&#160;then Ionis&#160;[***]. If Ionis [***] in accordance with <u>Section 2.7.2(c)i</u> ([***] Potential In-Licenses), then Ionis will [***]. Ionis may [***]. Within [***], Otsuka will [***]. If Otsuka [***] in accordance with this <u>Section
                2.7.2(c)ii</u> ([***] Potential In-Licenses), then such [***] and <u>Section 2.7.2(b)</u> (Collaboration In-Licenses) will apply, <font style="font-style: italic;">mutatis mutandis</font>. If Otsuka [***] in accordance with this <u>Section

                2.7.2(c)ii</u> ([***] Potential In-Licenses), then Otsuka [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="za1ec28c588e3486aa87742da6a016e80" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Right of First Negotiation for Follow-On Products</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7ed4c8155ac64f55a016f31fa9db1537" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.8.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">ROFN Exercise</font>. If, during the period from the Effective Date until the [***], Ionis intends to grant rights to a Third Party that include the right to Commercialize [***] designed to bind to the RNA
              encoding PKK for the treatment of HAE (any such compound, a &#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Product</font>&#8221;) in the Otsuka Territory, then Ionis will provide to Otsuka (a) notice of the proposed scope of
              Commercialization rights that Ionis proposes to grant and (b) an information package containing, to the extent such information is in Ionis&#8217; or its Affiliate&#8217;s Control: (i) summaries of [***] (ii) information about [***] (iii) a summary of
              [***] and (iv) [***] related to the Follow-On Product to the extent necessary or reasonably useful for Otsuka to evaluate whether to obtain rights with respect to Follow-On Product (&#8220;<font style="font-weight: bold; font-style: italic;">ROFN
                Notice and Package</font>&#8221;). Promptly thereafter, Ionis will provide a high-level presentation to the JSC relating to the Follow-On Product and the rights Ionis proposes to grant. Otsuka will have an exclusive right, exercisable no later
              than [***] after receipt of a ROFN Notice and Package from Ionis containing all information set forth in the foregoing clauses ((i) through (iv)) to the extent such information is in Ionis&#8217; or its Affiliate&#8217;s Control, to notify Ionis in
              writing as to whether Otsuka desires to negotiate for such rights to Commercialize such Follow-On Product in the Otsuka Territory (a &#8220;<font style="font-weight: bold; font-style: italic;">ROFN Exercise Notice</font>&#8221;). During such [***], Ionis
              will [***].</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">6</font></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;" noshade="noshade"></div>
    </div>
    <table id="zcae91a6e317445f79926ba60f3854664" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.8.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Negotiation</font>. If Otsuka provides a ROFN Exercise Notice to Ionis within such [***], then the Parties will negotiate in good faith for [***] from the date of Ionis&#8217; receipt of the ROFN Exercise Notice,
              or such longer period as may be agreed upon in writing by the Parties (the &#8220;<font style="font-weight: bold; font-style: italic;">ROFN Negotiation Period</font>&#8221;) the terms of a definitive agreement (or amendment to this Agreement) pursuant to
              which Ionis would grant to Otsuka the rights to Commercialize (and, as agreed by the Parties, to otherwise Exploit) such Follow-On Product in the Otsuka Territory. Neither Party will have any obligation to enter into any agreement or
              amendment to this Agreement granting rights to Otsuka to Commercialize or otherwise Exploit such Follow-On Product in the Otsuka Territory. If the ROFN Negotiation Period expires before the Parties have entered into an agreement or amendment
              to this Agreement with respect to Otsuka&#8217;s Commercialization or other Exploitation of such Follow-On Product in the Otsuka Territory, and if such ROFN Negotiation Period [***], then Ionis will have the right to negotiate and enter into an
              agreement with any Third Party with respect to a grant of rights to Exploit such Follow-On Product in the Otsuka Territory [***]. If Ionis does not grant rights to a Third Party that include the right to Commercialize such Follow-On Product
              in the Otsuka Territory [***], then the terms of this <u>Section 2.8</u> (Right of First Negotiation for Follow-On Products) will [***]. If the [***] expires before the Parties have entered into an agreement or amendment to this Agreement
              with respect to Otsuka&#8217;s Commercialization or other Exploitation of such Follow-On Product in the Otsuka Territory, then Ionis will have no further obligation to negotiate with Otsuka with respect to any grant of such rights to Otsuka and
              will be free to negotiate and enter into an agreement with any Third Party with respect to a grant of rights to Exploit such Follow-On Product in the Otsuka Territory.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd1ea9a634cca48dda71e8a8e1a602992" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">2.8.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Follow-On Product Activities</font>. If Ionis enters into an agreement with a Third Party granting any rights to Exploit a Follow-On Product, then all Development, Commercialization, and Medical Affairs
              activities related to such Follow-On Product (&#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Product Activities</font>&#8221;)<font style="font-weight: bold; font-style: italic;">&#160;</font>will be subject to the following: (a) [***]
              related to such Follow-On Product; and (b) Ionis and its Affiliates shall conduct the Follow-On Product Activities independently of the activities under this Agreement and [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 3</div>
    <div style="text-align: center; font-weight: bold;">TECHNOLOGY TRANSFER</div>
    <div>&#160;</div>
    <table id="z9728f0e947a14fcfabb3972f2733679a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">3.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Initial Know-How Transfer</font>. At a time period to be agreed upon by the Parties after the Effective Date, Ionis will provide and transfer, and in any event will initiate such transfer within [***] after
              the Effective Date, to Otsuka copies of the Ionis Know-How (other than Ionis Manufacturing and Analytical Know-How, the transfer of which will be conducted pursuant to <u>Section 7.4</u> (Manufacturing Technology Transfer)) that (a) exists
              on the Effective Date, (b) was not previously provided to Otsuka, and (c) is [***] to Develop, Commercialize or conduct Packaging and Labeling or Medical Affairs for a Licensed Product&#160; (such transfer, the &#8220;<font style="font-weight: bold; font-style: italic;">Initial Know-How Transfer</font>&#8221;). Ionis may make such Ionis Know-How available in such reasonable form as maintained by Ionis. In addition to the Initial Know-How Transfer, upon Otsuka&#8217;s reasonable request during the
              Term, Ionis will provide and transfer to Otsuka copies of or otherwise make available to Otsuka all Ionis Know-How (other than Ionis Manufacturing and Analytical Know-How) not previously provided to Otsuka hereunder to the extent such Ionis
              Know-How is [***] to Develop, Commercialize or conduct Packaging and Labeling or Medical Affairs for a Licensed Product, including in accordance with <u>Section 4.7</u> (Data Transfer), <u>Section 5.6</u> (Cooperation), <u>Section 6.1.2</u>
              (Commercialization in the Otsuka Territory), <u>Section 6.2</u> (Commercialization and Medical Affairs Reporting), and <u>Section 7.1.1</u> (Ionis Manufacturing) (the &#8220;<font style="font-weight: bold; font-style: italic;">Continuing Know-How
                Transfer</font>,&#8221; and together with the Initial Know-How Transfer, the &#8220;<font style="font-weight: bold; font-style: italic;">Technology Transfer</font>&#8221;). </div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z953f0ecd51434201ab9f87dd9d7a0517" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Technology Transfer Costs</font>. Ionis will conduct the Technology Transfer, and will provide consultation and assistance with [***] to provide support set forth in <u>Section 7.1.1</u> (Ionis
              Manufacturing) (any such consultation, assistance, or support provided by [***]. Ionis will [***] in connection with the Initial Know-How Transfer, including, for clarity, [***]. In addition, Ionis will [***] in providing Requested Assistance
              to Otsuka in connection with such Continuing Know-How Transfer, until [***] and, thereafter, [***]. After [***]. At all times, Otsuka will [***]. Ionis may [***] following receipt of such Regulatory Approval, to the extent [***]. Ionis shall
              [***]. Notwithstanding the foregoing, [***]. For clarity, the terms of this <u>Section 3.2</u> (Technology Transfer Costs) shall not apply with respect to [***] and, for clarity, the terms of this <u>Section 3.2</u> (Technology Transfer
              Costs) shall not apply to [***]. Notwithstanding any provision to the contrary, Ionis&#8217; obligations to conduct the Technology Transfer and provide Requested Assistance will not require Ionis to conduct any additional Clinical Trials or
              generate any additional data or information that is not expressly contemplated by the Cross-Territory Clinical Development Plan or Non-Clinical HAE Development Plan.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">7</font></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;" noshade="noshade"></div>
    </div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 4</div>
    <div style="text-align: center; font-weight: bold;">DEVELOPMENT</div>
    <div>&#160;</div>
    <table id="zfda358ada6df4f6baa80880405b517d1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Development Diligence Obligations</font>. Ionis will be responsible for conducting the activities under the Cross-Territory Clinical Development Plan and the Non-Clinical HAE Development Plan and will use
              Commercially Reasonable Efforts to carry out such activities. For clarity, Ionis shall not conduct any [***]. Otsuka will be responsible for conducting the activities under the Otsuka Territory-Specific Development Plan [***]. Each Party will
              conduct all Development activities for which it is responsible under this Agreement in a good scientific manner, in accordance with GLP and GCP, as applicable, and in compliance with Professional Requirements and Applicable Law.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7f52ee52b1d9462d8af0eee4c6cb9695" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">&#160;Development Plans</font><font style="color: rgb(0, 0, 0);">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z0f1b45ebf94146d0929b537e06d3d4d9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">4.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cross-Territory Clinical Development Plan</font>. The initial development plan for the clinical Development activities for both the Otsuka Territory and the Ionis Territory is set forth on <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 4.2.1</u> (such development plan as it may be modified in accordance with the terms and conditions of this Agreement, the &#8220;<font style="font-weight: bold; font-style: italic;">Cross-Territory
                Clinical Development Plan</font>&#8221;). The initial Cross-Territory Clinical Development Plan includes (and any updates to the Cross-Territory Clinical Development Plan will at all times include) all Clinical Trials that are intended to support
              obtaining or maintaining Regulatory Approval for any Licensed Product in both the Otsuka Territory and the Ionis Territory (any such Clinical Trials, &#8220;<font style="font-weight: bold; font-style: italic;">Cross-Territory Clinical Studies</font>&#8221;),
              including (a) all Cross-Territory Clinical Studies that are ongoing as of the Effective Date (the &#8220;<font style="font-weight: bold; font-style: italic;">Ongoing Cross-Territory Studies</font>&#8221;), (b) all Post-Approval Mandatory Studies that are
              (i) required to support maintaining Regulatory Approval for any Licensed Product in both the Otsuka Territory and the Ionis Territory and (ii) designed to meet the requirements of the EMA for maintaining Regulatory Approval of the Licensed
              Product in the Otsuka Territory (collectively ((i) and (ii)), &#8220;<font style="font-weight: bold; font-style: italic;">Post-Approval Cross-Territory Mandatory Studies</font>&#8221;), and (c) all future Cross-Territory Clinical Studies for [***]. From
              time to time during the Term, either Party may submit to the JSC any proposed update to the Cross-Territory Clinical Development Plan to include additional Cross-Territory Clinical Studies, including the study designs for such additional
              Cross-Territory Clinical Studies. In addition, each Party shall submit to the JSC (or a designated Subcommittee) reasonably in advance proposed updates to the Cross-Territory Clinical Development Plan to take into account changed
              circumstances, such as cessation of any Cross-Territory Clinical Study, or the need to amend any Cross-Territory Clinical Study, including amendments in response to Regulatory Authority requirements, for safety reasons or otherwise. The JSC
              will review, discuss, and determine whether to approve each update to the Cross-Territory Clinical Development Plan. Once reviewed and approved by the JSC, each update to the Cross-Territory Clinical Development Plan will automatically become
              effective and supersede the previous Cross-Territory Clinical Development Plan, as of the date of such approval by the JSC.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">8</font></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;" noshade="noshade"></div>
    </div>
    <table id="z23fed49bbae34cedae2c471f5cf7a186" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">4.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Non-Clinical HAE Development Plan</font>. The initial development plan for all CMC Development and non-clinical Development, in each case, required to obtain and maintain Regulatory Approval for the
              Licensed Product for the treatment of HAE in the Otsuka Territory is set forth on <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 4.2.2</u> (such development plan, as it may be modified in accordance with the terms and
              conditions of this Agreement, the &#8220;<font style="font-weight: bold; font-style: italic;">Non-Clinical HAE Development Plan</font>&#8221;). From time to time during the Term, either Party may submit to the JSC any proposed update to the Non-Clinical
              HAE Development Plan to include additional CMC Development or non-clinical Development activities required to obtain or maintain Regulatory Approval for the Licensed Product for the treatment of HAE in the Otsuka Territory. In addition, each
              Party shall submit to the JSC (or a designated Subcommittee) reasonably in advance proposed updates to take into account changed circumstances or the need to amend any CMC Development or non-clinical Development activities for the Licensed
              Product for the treatment of HAE in the Otsuka Territory. The JSC will review, discuss, and determine whether to approve each update to the Non-Clinical HAE Development Plan. Once reviewed and approved by the JSC, each update to the
              Non-Clinical HAE Development Plan will automatically become effective and supersede the previous Non-Clinical HAE Development Plan as of the date of such approval by the JSC.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z443b9ab7a28743e392dc31cb9f6ec274" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka Territory-Specific Development Plan</font>. Within [***] following the Effective Date, Otsuka will prepare and submit to the JSC a plan setting forth all Development activities that are intended to
              support obtaining or maintaining Regulatory Approval for the Licensed Products solely in the Otsuka Territory other than the activities set forth in the Non-Clinical HAE Development Plan (the &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory-Specific Development Plan</font>&#8221;). The JSC will review, discuss, and determine whether to approve the Otsuka Territory-Specific Development Plan. The Otsuka Territory-Specific Development Plan will, at all times
              during the Term, be consistent with the then-current Cross-Territory Clinical Development Plan, except to the extent such inconsistency is (a) necessary to conform with any written requirement from any Regulatory Authority or with any
              Applicable Law (including compliance requirements) in the Otsuka Territory or (b) approved by the JSC (by unanimous Party Vote). At least [***] during the Term (and more frequently as may be necessary), Otsuka will prepare an update to the
              Otsuka Territory-Specific Development Plan to amend or include additional Development activities to be conducted during the [***] Calendar Year that are intended to support obtaining or maintaining Regulatory Approval for the Licensed
              Products solely in the Otsuka Territory other than the activities set forth in the Non-Clinical HAE Development Plan (or otherwise update the Development activities under the Otsuka Territory-Specific Development Plan). The JSC will review,
              discuss, and determine whether to approve each update to the Otsuka Territory-Specific Development Plan. Once approved by the JSC, the Otsuka Territory-Specific Development Plan and each update thereto will automatically become effective and,
              in the case of an update, supersede the previous Otsuka Territory-Specific Development Plan as of the date of such approval. Notwithstanding the foregoing or anything to the contrary in this Agreement, the Otsuka Territory-Specific
              Development Plan will at all times include Development activities that are (i) necessary to obtain and maintain Regulatory Approval for at least one Licensed Product in [***] consistent with Otsuka&#8217;s obligations under <u>Section 4.1</u>
              (Development Diligence Obligations) and (ii) not included in the Cross-Territory Clinical Development Plan or the Non-Clinical HAE Development Plan.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z8445a6c84ab7430caf62b9729dc4f15c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Development Costs</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z827478e8241a49d097e28094f5da9c61" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">4.4.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Overview</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zbe77250efa744a5b81af6b8d4a7c875c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Costs</font>. Ionis will be [***] responsible for all costs and expenses incurred in connection with the performance of the [***]. In addition, Ionis will be [***] responsible for all costs and
              expenses incurred in connection with the performance of all activities under the [***].</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">9</font></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;" noshade="noshade"></div>
    </div>
    <table id="ze3222ed9a1f94c08b0067779f26f8992" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka Costs</font>. Otsuka will be [***] responsible for all costs and expenses incurred in connection with the performance of all activities under the [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z94ad20eac21d413098c691f5d8fb6631" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Shared Development Costs</font><font style="font-style: italic;">. </font>With respect to (i) all Post-Approval Cross-Territory Mandatory Studies for the treatment of HAE that are included in the
              Cross-Territory Clinical Development Plan as of the Effective Date] and (ii) [any other Post-Approval Cross-Territory Mandatory Studies for the treatment of HAE or any Future Cross-Territory Studies, in each case, that are added to the
              Cross-Territory Clinical Development Plan in accordance with <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan), the Parties will share, [***], in each case, in accordance with the Cross-Territory Clinical Development Plan and
              Shared Development Budget (such costs, &#8220;<font style="font-weight: bold; font-style: italic;">Shared Cross-Territory Development Costs</font>&#8221;) in accordance with the terms of <u>Section 4.4.3</u> (Shared Cross-Territory Development Costs).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">4.4.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Shared Development Budget; Cost Overruns</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z611f8d7e8aca4b938934ff81e2a70ac8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Shared Development Budget</font>. The initial budget for the Shared Cross-Territory Development Costs (such budget as it may be modified in accordance with the terms and conditions of this Agreement, the &#8220;<font style="font-weight: bold; font-style: italic;">Shared Development Budget</font>&#8221;) for the Post-Approval Cross-Territory Mandatory Studies that are included in the Cross-Territory Clinical Development Plan as of the Effective Date is set
              forth in <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 4.4.2</u> (Shared Development Budget). With respect to each other Post-Approval Cross-Territory Mandatory Study for the treatment of HAE or Future Cross-Territory
              Study that is subject to cost sharing by the Parties in accordance with <u>Section 4.4.1(c)</u> (Shared Development Costs), the JSC will develop, discuss, and determine whether to approve an update to the Shared Development Budget at the
              time the JSC reviews, discusses, and determines whether to approve the update to the Cross-Territory Clinical Development Plan applicable to such additional Cross-Territory Clinical Study. Any update to the Shared Development Budget will at
              all times include a detailed written budget for the performance of all Future Cross-Territory Studies and any additional Post-Approval Cross-Territory Mandatory Studies for the treatment of HAE, in each case, that are included in the
              Cross-Territory Clinical Development Plan (as updated). From time to time during the Term, either Party may submit to the JSC any proposed update to the Shared Development Budget, including in connection with any update to the Cross-Territory
              Clinical Development Plan or to address a potential Cost Overrun. The JSC will review, discuss, and determine whether to approve each update to the Shared Development Budget. Once reviewed and approved by the JSC, each update to the Shared
              Development Budget will automatically become effective and supersede the previous Shared Development Budget, as of the date of such approval by the JSC.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">10</font></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;" noshade="noshade"></div>
    </div>
    <table id="z4b1bd69bcfa14eeead71ec8acda7a32c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cost Overruns</font>. Ionis [***] for a given Calendar Year [***] for such Calendar Year. Ionis will notify the JSC (or any designated Subcommittee) without undue delay if it reasonably anticipates that the
              Shared Cross-Territory Development Costs are reasonably likely to exceed the then-current Shared Development Budget by more than [***] (a &#8220;<font style="font-weight: bold; font-style: italic;">Cost Overrun</font>&#8221;). Ionis will include [***]
              and, to the extent reasonably possible, will [***]. Thereafter, the JSC (or designated Subcommittee) shall promptly hold an ad-hoc meeting to evaluate whether there are mitigation measures to prevent the Cost Overrun, and if not, the JSC (or
              designated Subcommittee) will discuss what steps to take to address such Cost Overrun, including updating the Shared Development Budget or the Cross-Territory Clinical Development Plan, as applicable. If the JSC does not approve an update to
              the Shared Development Budget to reflect the anticipated Cost Overrun, then [***] and, to the extent [***]. For clarity, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z2eb64338e68243abb979df93f8471f10" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">4.4.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Shared Cross-Territory Development Costs</font>. The Parties will share, at the [***], all Shared Cross-Territory Development Costs incurred by or on behalf of Ionis or its Affiliates in accordance with the
              Cross-Territory Clinical Development Plan and the amount budgeted therefor in the Shared Development Budget,<font style="font-style: italic;"> plus</font> [***] (&#8220;<font style="font-weight: bold; font-style: italic;">Eligible Cross-Territory
                Development Costs</font>&#8221;). No later than [***] after the end of each Calendar Quarter, Ionis will deliver to Otsuka a written report specifying in reasonable detail the Eligible Cross-Territory Development Costs incurred by or on behalf of
              Ionis during such Calendar Quarter, together with reasonable supporting documentation (the &#8220;<font style="font-weight: bold; font-style: italic;">Development Cost Share Notice</font>&#8221;) and an invoice (and, if there has been any change to a
              Payment Form previously submitted, or if a previously submitted Payment Form has expired, an updated Payment Form) for Otsuka&#8217;s [***] share of such Eligible Cross-Territory Development Costs. No later than [***] after Otsuka&#8217;s receipt of the
              Development Cost Share Notice and invoice (and updated Payment Form, if applicable) for such Calendar Quarter, Otsuka will make a balancing payment to Ionis equal to [***] of the total Eligible Cross-Territory Development Costs to effect the
              [***] for such Eligible Cross-Territory Development Costs; <font style="font-style: italic;">provided</font> that, if Otsuka disputes any invoiced amount, then Otsuka will pay the undisputed invoiced amount within such [***] and will pay any
              disputed amounts within [***] following resolution of the dispute and determination that such amounts are owed.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zfe074d0c24ed4213ad99f236fcac6ed0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">4.4.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Future Cross-Territory Studies for [***]</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z1049092813334351a99382cf80f04951" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Shared Costs</font>. At any time during the Term, either Party may propose that the Parties clinically Develop a Licensed Product [***]. Such Party will submit a proposal to the JSC setting forth the
              proposed clinical Development activities for such [***] and a timeline and budget for such activities (a &#8220;[***]&#8221;). The JSC will review, discuss, and determine whether to approve such [***], either as proposed or as may be revised by agreement
              of the JSC, within [***] of the submission thereof. If the JSC approves such [***], as proposed or as revised per the agreement of the Parties, then (i) the JSC will approve an update to the Cross-Territory Clinical Development Plan in
              accordance with <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan) and to the Shared Development Budget in accordance with <u>Section 4.4.2(a)</u> (Shared Development Budget) to include any Future Cross-Territory Studies for
              such [***] and (ii) the Parties will share the cost of any Eligible Cross-Territory Development Costs incurred in connection with the performance of such Future Cross-Territory Studies in accordance with <u>Section 4.4.3</u> (Shared
              Cross-Territory Development Costs).</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">11</font></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;" noshade="noshade"></div>
    </div>
    <table id="z707ffcfac72e49509ad0694ad462d202" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">[***] by Ionis</font>. If the JSC does not approve [***] for a given [***] or does not approve an updated Cross-Territory Clinical Development Plan in accordance with <u>Section 4.2.1</u> (Cross-Territory
              Clinical Development Plan) or Shared Development Budget in accordance with <u>Section 4.4.2(a)</u> (Shared Development Budget) to include the Future Cross-Territory Studies for such [***], then (i) Ionis will have the right, but not the
              obligation, to proceed with the Development of such [***] in the Territory as contemplated by [***] with such modifications as Ionis deems appropriate [***] (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis </font>[***]&#8221;) and such
              Development will be conducted outside the Cross-Territory Clinical Development Plan; and (ii) notwithstanding the licenses, rights of reference, and other rights granted to Otsuka under this Agreement, Otsuka will not have any license or
              rights to use any Ionis [***] (including any right of reference to use such Ionis [***] contained in the related Regulatory Submissions by Ionis and notwithstanding the inclusion of any such data in the Ionis Technology) in support of any
              Regulatory Submissions or Regulatory Approval for the Licensed Product in the Otsuka Territory or in the Commercialization of such Licensed Product in the Otsuka Territory, unless and until [***], <font style="font-style: italic;">provided</font>
              that Otsuka may use safety data in connection with such Ionis [***] solely to satisfy any safety-related reporting obligations to Regulatory Authorities related to Licensed Products in the Otsuka Territory without [***]. For clarity, Ionis
              [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z223c30cc6baa4172b39f983e65b891a6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka Opt-In</font>. If Ionis conducts any Ionis [***] pursuant to <u>Section 4.4.4(b)</u> ([***] by Ionis), then Ionis shall provide Development reports to Otsuka related to such Ionis [***] in
              accordance with <u>Section 4.5</u> (Development Reports), and Otsuka shall have the right, [***] to opt-in with respect to such Ionis [***] in accordance with this <u>Section 4.4.4(c)</u> (Otsuka Opt-In). Upon Otsuka&#8217;s written request,
              Ionis shall provide to Otsuka a written report of the Internal Costs and External Costs, in each case, incurred directly by or on behalf of Ionis or its Affiliates as of the date of such written request in the performance of such Ionis [***]
              (the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis </font>[***] <font style="font-weight: bold; font-style: italic;">Costs</font>&#8221;). Such written report shall include supporting documentation of the External Costs included
              within the Ionis [***] Costs. Otsuka shall have the right, exercisable during the [***] period after receipt of such report, to provide notice to Ionis that Otsuka wishes to share the costs of such Ionis [***] (&#8220;<font style="font-weight: bold; font-style: italic;">Opt-In Notice</font>&#8221;). Following the receipt of an Opt-In Notice, Ionis shall provide an invoice to Otsuka for [***] of such Ionis [***] (&#8220;<font style="font-weight: bold; font-style: italic;">Opt-In Fee</font>&#8221;)
              as follows: [***]. Otsuka shall pay the Opt-In Fee within [***] after receipt of such invoice and supporting documentation; <font style="font-style: italic;">provided</font> that, if Otsuka disputes any invoiced amount, then Otsuka will pay
              the undisputed invoiced amount within such [***] and will pay any disputed amounts within [***] following resolution of the dispute and determination that such amounts are owed. Following Otsuka&#8217;s payment of the Opt-In Fee, (A) the Ionis
              [***] shall be deemed a Future Cross-Territory Study and will be added to the Cross-Territory Clinical Development Plan, (B) the Parties will share, [***], all Internal Costs reasonably incurred and External Costs incurred, in each case,
              directly by or on behalf of Ionis or its Affiliates in the performance of the Ionis [***] from the date on which Ionis provides a written report of the Ionis [***] Costs, (C) the applicable Ionis [***] shall be included within Ionis Know-How
              and subject to the licenses in <u>Section 2.1</u> (License Grants to Otsuka), and (D) the Ionis [***] included in related Regulatory Submissions will be subject to Otsuka&#8217;s right of use and right of reference provided in <u>Section 5.9</u>
              (Right of Reference).]</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">12</font></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;" noshade="noshade"></div>
    </div>
    <table id="z75fc064e6ad1489989cd0c76205910c5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Development Reports</font>. At each JSC meeting, Ionis and Otsuka will each provide the JSC with a written summary of the activities conducted by or on behalf of such Party under, as applicable, the
              Cross-Territory Clinical Development Plan, the Non-Clinical HAE Development Plan, and the Otsuka Territory-Specific Development Plan, and with respect to Ionis, [***], in each case, since the last JSC meeting, including patient enrollment,
              the ongoing status, and material results of all Clinical Trials for the Licensed Products conducted by or on behalf of such Party. Each Party will also promptly provide written notice to the other Party and keep the other Party reasonably
              informed, through the JSC or Alliance Managers, of any significant Development events under the Cross-Territory Clinical Development Plan, the Non-Clinical HAE Development Plan, or the Otsuka Territory-Specific Development Plan, and with
              respect to Ionis, any additional Development activities conducted by or on behalf of Ionis or any of its Affiliates for the Licensed Product that are not set forth in the Cross-Territory Clinical Development Plan or the Non-Clinical HAE
              Development Plan, in each case, that [***] the Development activities of the other Party under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z617c1a154e0c40529cf158b8b2bed9b4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Development Records; Cooperation</font>. Each Party and its Affiliates will maintain written or electronic records, in sufficient detail, in a good scientific manner, in accordance with Applicable Law
              (including GLP, GCP, and GMP, as applicable), and appropriate for regulatory and patent purposes, and that are complete and accurate and reflect all Development work performed and results achieved, in each case, by or on behalf of such Party
              and its Affiliates under, as applicable, the Cross-Territory Clinical Development Plan, the Non-Clinical HAE Development Plan, and the Otsuka Territory-Specific Development Plan, and with respect to Ionis, [***]. Each Party shall retain such
              records for at least three years after the end of the Term or for such longer period as may be required by Applicable Law. The Parties will cooperate with each other to achieve the Development objectives contemplated herein in a timely,
              accurate, and responsive manner. Without limiting the foregoing, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="za8d4ffdb7183445ebf21aae668160879" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Data Transfer</font>. Upon Otsuka&#8217;s reasonable request, Ionis shall provide to Otsuka, [***] notwithstanding the terms of <u>Section 3.2</u> (Technology Transfer Cost), true and complete copies of all
              written, graphic or electronic embodiments of non-clinical data and clinical data generated by or on behalf of Ionis or any of its Affiliates in connection with the Development of Licensed Products, including all draft and final protocols and
              final study reports and raw data, in each case, to the extent such data is (a) Controlled by Ionis or its Affiliates and (b) [***] to Exploit a Licensed Product. [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 5</div>
    <div style="text-align: center; font-weight: bold;">REGULATORY AFFAIRS</div>
    <div>&#160;</div>
    <table id="z36c864520fd74c5bb391f71fc4d5a17e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Regulatory Responsible Party</font>. Ionis will be the Regulatory Responsible Party for the Licensed Products in the Ionis Territory. Otsuka will be the Regulatory Responsible Party for the Licensed
              Products in the Otsuka Territory, <font style="font-style: italic;">provided </font>that, Ionis shall have the right to conduct regulatory activities in the Otsuka Territory, including interacting with Regulatory Authorities, solely with
              respect to (a) the Development activities for the Licensed Products in the Otsuka Territory for which Ionis is responsible under the Cross-Territory Clinical Development Plan and the Non-Clinical HAE Development Plan and (b) the Manufacturing
              activities for the Licensed Products for which Ionis is responsible in accordance with <u>Article 7</u> (Manufacturing), in each case subject to the remainder of this <u>Article 5</u> (Regulatory Affairs) (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#160;<font style="font-weight: bold; font-style: italic;">Regulatory Activities</font>&#8221;). Subject to the obligations in this <u>Article 5</u> (Regulatory Affairs), the Regulatory Responsible Party will be
              responsible for, and [***] all Regulatory Submissions, communications, and other dealings with the Regulatory Authorities relating to the Licensed Products in the applicable Territory, and for seeking and maintaining all Regulatory Approvals
              with respect to the Licensed Product in the applicable Territory. The Regulatory Responsible Party will not be required to delay any submission, correspondence, or communication with any Regulatory Authorities in a manner that affects such
              Regulatory Responsible Party&#8217;s ability to comply with any Regulatory Authority requirement or deadline or Applicable Law in such jurisdiction. For clarity, Otsuka or its designee shall be the holder of all Regulatory Approvals for the
              Licensed Product in the Otsuka Territory and will own all Regulatory Submissions in the Otsuka Territory, and Ionis or its designee shall be the holder of all Regulatory Approvals for the Licensed Product in the Ionis Territory and will own
              all Regulatory Submissions in the Ionis Territory. Otsuka will only [***] and will not [***].</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">13</font></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;" noshade="noshade"></div>
    </div>
    <table id="z5555d64c1fa94eaabea8918761293ef7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Regulatory Subcommittee</font>. Within [***] after the Effective Date, the Parties will establish, through the JSC, a Subcommittee to (a) oversee the preparation and submission of any MAA for a Licensed
              Product in the Otsuka Territory and (b) coordinate the regulatory responsibilities between the Parties in the Otsuka Territory, which allocation will be consistent with this <u>Article 5</u> (Regulatory Affairs) (such Subcommittee, the &#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Subcommittee</font>&#8221;). The Regulatory Subcommittee will review and comment on any proposed MAA application for a Licensed Product sufficiently in advance of the filing or submission
              thereof by Otsuka, and Otsuka will [***] any comments received from the Regulatory Subcommittee. The Regulatory Subcommittee will meet as often as necessary to carry out the activities described in this <u>Section 5.2</u> (Regulatory
              Subcommittee) and the terms of <u>Section 8.2</u> (Additional Committees) will apply to the Regulatory Subcommittee.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z005d8425b74f447eba8b396c5c216fae" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Correspondences with Regulatory Authorities</font>. Otsuka shall be solely responsible for communications with Regulatory Authorities in the Otsuka Territory regarding the Licensed Product and in no event
              will [***] regarding the Licensed Product in the Otsuka Territory, except in connection with [***], and subject to the remainder of this <u>Section 5.3</u> (Correspondences with Regulatory Authorities). Ionis will [***]. In addition, Ionis
              will [***]. Furthermore, upon Otsuka&#8217;s reasonable request and at [***], Ionis will [***]. The Regulatory Responsible Party will provide the other Party with (a) copies of any material written correspondence submitted to or received from (i)
              with respect to Otsuka, the EMA or any other Regulatory Authority in the Otsuka Territory, and (ii) with respect to Ionis, the FDA or any other Regulatory Authority in the U.S., and (b) summaries of any material oral communications with such
              Regulatory Authority in clause (a), in each case ((a) and (b)), relating to Regulatory Submissions in support of Development of the Licensed Products in such jurisdiction or country, reasonably promptly after receipt or delivery by such
              Regulatory Responsible Party of such correspondence or communication, as the case may be (but in any event, no later than [***] after receipt or delivery).</div>
          </td>
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    </table>
    <div>&#160;</div>
    <table id="z90f924fde8d64c51976e773d80eab7c4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Regulatory Meetings</font>. Ionis will [***] meetings pertaining to Regulatory Submissions for the Licensed Products relating to the Ionis Regulatory Activities [***] in the Otsuka Territory] to the extent
              not prohibited by Applicable Law or the applicable Regulatory Authority. At Otsuka&#8217;s request, Ionis will [***]. With respect to all other meetings with any Regulatory Authority in the Otsuka Territory in support of Development of the Licensed
              Products, (a)&#160; Ionis will have the right, but not the obligation, [***] to attend such meetings [***] and (b) at Otsuka&#8217;s reasonable request, Ionis will [***] and Otsuka will [***]. Further, Ionis will [***], unless Ionis reasonably believes
              that [***], and will not [***] except as (a) required by Applicable Law, (b) permitted pursuant to <u>Section 12.4.1(b)</u> (Permitted Circumstances) or <u>Section 12.4.1(c)</u> (Permitted Circumstances), or (c) authorized by Otsuka in
              writing. For clarity, the terms of this <u>Section 5.4</u> (Regulatory Meetings) will apply solely with respect to any meetings with any Regulatory Authority in the Otsuka Territory in support of Development of the Licensed Products and do
              not apply to any meetings with Regulatory Authorities in the Otsuka Territory pertaining to [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd2008e21dbac400ea2154603d69b97b7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Regulatory Submissions</font>. Each Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Filing Party</font>&#8221;) will provide the other Party with a copy of [***] (including, [***]) that the
              Filing Party intends to file with or submit to any Regulatory Authority in support of Development in the Otsuka Territory for the other Party&#8217;s review and comment sufficiently in advance of the Filing Party&#8217;s filing or submission thereof. The
              Filing Party will [***] any reasonable comments received from the other Party into such Regulatory Submissions. In addition and notwithstanding <u>Section 3.2</u> (Technology Transfer Cost), Ionis will provide to Otsuka, [***].</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">14</font></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;" noshade="noshade"></div>
    </div>
    <table id="zdd1e0830e985473a873c07558a398d07" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cooperation</font>. The Parties will cooperate with each other to achieve the regulatory objectives contemplated herein in a timely, accurate, and responsive manner. Without limiting the foregoing or the
              terms of <u>Section 5.5</u> (Regulatory Submissions), at Otsuka&#8217;s reasonable request, Ionis will [***] of the Licensed Products in the Otsuka Territory or for obtaining and maintaining Regulatory Approval of the Licensed Products in the
              Otsuka Territory. If Otsuka receives any inquiry from a Regulatory Authority in the Otsuka Territory pertaining to any activities for which Ionis is responsible hereunder (including Cross-Territory Clinical Studies, non-clinical or CMC
              Development or Manufacturing (prior to the Manufacturing Handover Date)), then notwithstanding <u>Section 3.2</u> (Technology Transfer Cost), upon Otsuka&#8217;s request, Ionis will, [***]. In addition, upon Otsuka&#8217;s reasonable request, Ionis
              shall provide [***] in the Otsuka Territory (&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Support</font>&#8221;). Ionis will provide all Regulatory Support [***] until [***]. Thereafter, [***], Ionis will [***], and [***], Ionis
              will [***]. At all times, Otsuka will [***]. Ionis may [***]&#160; (i) [***], and (ii) [***] and, in each case ((i) and (ii)), [***]&#160; (and, with respect to [***]) therefor [***]. For clarity, if Otsuka requests Regulatory Support in connection
              with [***], Ionis shall provide such Regulatory Support [***], and Otsuka [***]. Notwithstanding any provision to the contrary, this <u>Section 5.6</u> (Cooperation) will not require Ionis to conduct any additional Clinical Trials or
              generate any additional data or information that is not expressly contemplated by the Cross-Territory Clinical Development Plan or Non-Clinical HAE Development Plan.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z24cd6e9589ad4479991087eca5fda310" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cost of Regulatory Activities</font>. Except to the extent specified otherwise in this <u>Article 5</u> (Regulatory Affairs), each Party will be responsible for all costs and expenses incurred in
              connection with its activities under this <u>Article 5</u> (Regulatory Affairs), including the preparation or maintenance of Regulatory Submissions and Regulatory Approvals with respect to the Licensed Products for which it is responsible,
              including any filing fees and, with respect to Ionis, including all costs and expenses of Ionis Regulatory Activities and all costs and expenses related to the ASMF (if filed) and other regulatory affairs related to Manufacturing of Licensed
              Products, which in each case will be borne solely by Ionis.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zcf98423c6b404864875febbfe4c5643b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Harmful Actions</font>. If [***], then such first Party will have the right to bring such matter to the attention of the JSC and the Parties will discuss in good faith to resolve such concern. Without
              limiting the foregoing and notwithstanding any provision to the contrary in this Agreement, Otsuka will not [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z77e3744b062348f692d5a3e1115ae0ce" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Right of Reference</font>. Subject to the rules of the relevant Regulatory Authority and the terms of this Agreement, including <u>Section 4.4.4(b)</u> ([***] by Ionis), each Party hereby grants to the
              other Party 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, and a right to copy, access, and otherwise use, all
              information and data relating to the Licensed Products in any Regulatory Submission or Regulatory Approval Controlled by the grantor Party during the Term (including, with respect to the grant to Otsuka, a right of reference to Ionis&#8217; Drug
              Master File and ASMF, if filed), solely for the other Party&#8217;s or its Affiliates&#8217; use in the Development or Commercialization of the Licensed Products in the other Party&#8217;s Territory in accordance with this Agreement. All such information and
              data contained in any such Regulatory Submissions or Regulatory Approvals will be considered Confidential Information of the grantor Party and subject to the terms of <u>Article 12</u> (Confidentiality). If requested by the grantee Party,
              the grantor Party will provide a signed statement to this effect in accordance with 21 C.F.R. &#167; 314.50(g)(3) (or any successor rule or analogous Applicable Law outside of the United States) to give effect to the intent of this <u>Section 5.9</u>
              (Right of Reference).</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">15</font></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;" noshade="noshade"></div>
    </div>
    <table id="z6669b3297c4c4576b9729f263cc21c40" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Pharmacovigilance; Safety Information</font>. Each Party will cooperate with the other Party, at no cost to the other Party (notwithstanding <u>Section 3.2</u> (Technology Transfer Cost)), with regard to
              the reporting and handling of safety information involving the Licensed Products in accordance with Applicable Law, regulatory requirements, and regulations on pharmacovigilance and clinical safety. Otsuka will be responsible for all
              processing of information related to any adverse events for the Licensed Products in the Otsuka Territory and Ionis will be responsible for all processing of information related to any adverse events for the Licensed Products in the Ionis
              Territory, in each case, including any information regarding such adverse events that is received from a Third Party. Each Party will provide to the other Party in a timely manner the relevant safety information it receives (either directly
              or indirectly) related to the Licensed Products. At an appropriate time as agreed upon by the Parties following the Effective Date, but in any event prior to the [***], the Parties will negotiate in good faith and enter into a
              Pharmacovigilance Agreement related to the Licensed Products, which will define the pharmacovigilance responsibilities of the Parties and include safety data exchange procedures governing the exchange of information affecting the class and
              products (<font style="font-style: italic;">e</font>.<font style="font-style: italic;">g</font>., Serious Adverse Events, emerging safety issues) to enable each Party to comply with all of its legal and regulatory obligations related to such
              Licensed Product. Prior to the execution of the Pharmacovigilance Agreement, each Party will have the right, upon reasonable notice to the other Party, to [***]. Ionis will own and maintain the global safety database for the Licensed Products
              at [***], <font style="font-style: italic;">provided</font> that at Otsuka&#8217;s reasonable request, Ionis will run queries of such global safety database and will provide copies of the data contained in such global safety database to the extent
              necessary or reasonably useful to the Development and Commercialization of the Licensed Product in the Otsuka Territory. As part of the negotiation of the Pharmacovigilance Agreement, the Parties will [***], taking into account that Ionis
              will own and maintain the global safety database, and the Parties&#8217; determination of such matter will be set forth in the Pharmacovigilance Agreement. Subject to compliance with Applicable Law, each Party hereby agrees to comply with its
              respective obligations under the Pharmacovigilance Agreement as the Parties may agree to modify it from time to time, and to cause its (sub)licensees to comply with such obligations. If there is a conflict between the terms and conditions of
              this Agreement and any terms and conditions of the Pharmacovigilance Agreement, then the terms and conditions of the Pharmacovigilance Agreement will govern with respect to any pharmacovigilance matters and this Agreement will govern with
              respect to any other matters.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z987ce436848a4be4b30f0e4e0f1e3df3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.11</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Pharmacovigilance Subcommittee</font>. The JSC shall establish a joint pharmacovigilance subcommittee (the &#8220;<font style="font-weight: bold; font-style: italic;">PV Subcommittee</font>&#8221;) at an appropriate
              time, but in any event prior to the [***]. In addition to any other matters that the JSC may delegate to the PV Subcommittee, the PV Subcommittee shall provide a forum for the Parties to discuss, share information, and escalate and attempt to
              resolve safety issues regarding the Licensed Product, and any other pharmacovigilance matters, worldwide. The PV Subcommittee will meet as often as necessary to carry out such activities, and the terms of <u>Section 8.2</u> (Additional
              Committees) will apply to the PV Subcommittee.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z4d64d8efb8d14212b13f39fdb230b002" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.12</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Internal Oligonucleotide Safety Database</font>.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">16</font></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;" noshade="noshade"></div>
    </div>
    <table id="z81c07a772a054ab7982a36d22969d8ec" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">5.12.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Ionis maintains an internal database that includes information regarding the tolerability of its drug compounds, individually and as a class, including information discovered during non-clinical and clinical Development (the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Internal Oligonucleotide Safety Database</font>&#8221;). To maximize understanding of the safety profile and pharmacokinetics of Ionis compounds, (a) Ionis will have the right to use any
              safety-related information provided by Otsuka pursuant to the Pharmacovigilance Agreement or this <u>Section 5.12</u> (Ionis Internal Oligonucleotide Safety Database) to maintain the Ionis Internal Oligonucleotide Safety Database and (b)
              Otsuka will cooperate, at no cost to Ionis, with Ionis&#8217; reasonable requests in connection with populating the Ionis Internal Oligonucleotide Safety Database, including by providing Ionis with reasonably requested safety-related supporting
              data and answering any follow-up questions reasonably requested by Ionis or its Affiliates in connection with any information provided under the Pharmacovigilance Agreement, in each case to the extent such data and answers are reasonably
              available to Otsuka. In addition, with respect to Clinical Trials of the Licensed Products conducted by or on behalf of Otsuka pursuant to the Otsuka Territory-Specific Development Plan (if any), Otsuka will provide Ionis with copies of
              annual safety updates filed with each IND and the safety sections of any final Clinical Trial reports within [***] following the date such information is filed, as applicable. All such information disclosed by Otsuka to Ionis will be Otsuka
              Confidential Information; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that so long as Ionis does not disclose the identity of a Licensed Product or Otsuka&#8217;s identity, Ionis may
              disclose any such Otsuka Confidential Information to (i) Ionis&#8217; other partners if such information is regarding class generic properties of oligonucleotides, (ii) any Third Party that contributes to the populating of the Ionis Internal
              Oligonucleotide Safety Database, or (iii) any Regulatory Authority. Otsuka will also cause its Affiliates and Sublicensees to comply with this <u>Section 5.12</u> (Ionis Internal Oligonucleotide Safety Database).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z8f0cd56b01ee4892848c5ff76be1a477" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">5.12.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>From time to time, Ionis utilizes the information in the Ionis Internal Oligonucleotide Safety Database to conduct analyses to keep Ionis and its partners informed regarding class generic properties of oligonucleotides, including with
              respect to safety. As such, if and when Ionis identifies safety or other related issues that may be relevant to a Licensed Product (including any potential class-related toxicity), Ionis will promptly inform Otsuka of such issues and provide
              the data supporting Ionis&#8217; conclusions.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7028f5d4aed743d384cdfddbce998457" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.13</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Recall, Withdrawal, or Field Alerts</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zda5b00dc2dcc493cb59ddeef41bbcbcf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">5.13.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Notification and Determination</font>. Each Party will notify the other Party immediately, and promptly confirm such notice in writing, if it obtains information indicating that any Licensed Product may be
              subject to a recall (whether voluntary or mandated), corrective action, or similar regulatory action by any Governmental Authority or Regulatory Authority (a &#8220;<font style="font-weight: bold; font-style: italic;">Remedial Action</font>&#8221;). The
              Parties will assist each other in gathering and evaluating such information as is necessary to determine the necessity of conducting a Remedial Action with respect to the applicable Territory, and otherwise reasonably cooperate with each
              other with respect to such Remedial Action or potential Remedial Action. Ionis will have sole discretion and final decision-making authority with respect to, and control over, any Remedial Action in the Ionis Territory, including any decision
              to commence such Remedial Action in the Ionis Territory. Otsuka will have sole discretion and final decision-making authority with respect to, and control over, any Remedial Action in the Otsuka Territory, including any decision to commence
              such Remedial Action in the Otsuka Territory; <font style="font-style: italic;">provided that </font>if Ionis notifies Otsuka of [***] that Ionis reasonably believes could give rise to a Remedial Action, then Otsuka will initiate such
              Remedial Action in accordance with Ionis&#8217; request and at [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc89b0600c9874be09329177a82f467e6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">5.13.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cost Allocation</font>. Except as otherwise set forth in <u>Section 5.13.1</u> (Notification and Determination), all costs directly associated with implementing a Remedial Action with respect to a Licensed
              Product will be allocated between Ionis and Otsuka as follows:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zcc5b7c9dd88c43dc96560c3b8c09fd04" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
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          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If, and to the extent, that the Remedial Action arises as a result of [***], then [***] will bear all such costs and expenses; and</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">17</font></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;" noshade="noshade"></div>
    </div>
    <table id="z8855653c418e4305ad72e282b37c34a5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>in all other cases, Ionis will be responsible for such costs and expenses for such Licensed Product in the Ionis Territory and Otsuka will be responsible for such costs and expenses for such Licensed Product in the Otsuka Territory.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 6</div>
    <div style="text-align: center; font-weight: bold;">COMMERCIALIZATION AND MEDICAL AFFAIRS</div>
    <div>&#160;</div>
    <table id="zcea6b631439a408d840cbb38caf38543" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Commercialization Responsibilities for Licensed Product</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5de3d822dae64026b8199f9aa223bfa9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">6.1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Commercialization in the Ionis Territory</font>. Subject to the last sentence of <u>Section 6.4</u> (Global Brand Strategic and Operating Plan) and the last sentence of <u>Section 6.7.1</u> (Global
              Medical Affairs Plan), and without limiting Ionis&#8217; obligations under this <u>Article 6</u> (Commercialization and Medical Affairs), Ionis and its Affiliates will have [***] with respect to the Commercialization of the Licensed Products in
              the Ionis Territory, including, if applicable, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5f7cfd6bc7294b14a9399e6ca2282918" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">6.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Commercialization in the Otsuka Territory</font>. Subject to the terms and conditions of this Agreement, and without limiting Otsuka&#8217;s obligations under this <u>Article 6</u> (Commercialization and Medical
              Affairs), Otsuka and its Affiliates will have [***] with respect to the Commercialization of the Licensed Products in the Otsuka Territory, including [***]. Upon Otsuka&#8217;s reasonable request, Ionis shall [***], including [***], and Ionis will
              [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z70cc50bf6e9e4ecba3041f5891a82045" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">6.1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Coordination of Commercialization Activities</font>.<font style="font-weight: bold;">&#160;</font>The Parties will coordinate global Commercialization activities with respect to Commercialization of the Licensed
              Products in each Party&#8217;s Territory through the JSC, as further set forth in <u>Section 8.1</u> (Joint Steering Committee) and this <u>Article 6</u> (Commercialization and Medical Affairs).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zed8a8ebe7aa94616b51ec979af165583" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Commercialization and Medical Affairs Reporting</font>. At each JSC meeting following the first Regulatory Approval for a Licensed Product in the Otsuka Territory, Otsuka will provide to the JSC a
              high-level summary (which may be in the form of a slide presentation) of the material Commercialization and Medical Affairs activities conducted by Otsuka or its Affiliates or Sublicensees for the Licensed Products in the Otsuka Territory
              during the period since the last JSC meeting and the material Commercialization and Medical Affairs activities expected to be conducted by Otsuka or its Affiliates, or Sublicensees in the Otsuka Territory for the Licensed Products during the
              period from the date of such update until the next JSC meeting, and shall answer any reasonable questions asked by Ionis to enable Ionis to assess Otsuka&#8217;s compliance with its Commercialization diligence obligations set forth in <u>Section
                6.6</u> (Otsuka Commercialization Diligence Obligations). In addition, no later than [***], Otsuka will provide to the JSC a report of the forecasted Net Sales anticipated to be generated by Otsuka or its Affiliates, licensees, or
              Sublicensees in the Otsuka Territory during the upcoming Calendar Year, which forecast will be broken down on a country-by-country basis. At each JSC meeting following the first Regulatory Approval for a Licensed Product in the Ionis
              Territory, Ionis will provide to the JSC a high-level summary (which may be in the form of a slide presentation) of the material Commercialization and Medical Affairs activities conducted by Ionis or its Affiliates for the Licensed Products
              in the Ionis Territory during the period since the last JSC meeting and the material Commercialization and Medical Affairs activities expected to be conducted by Ionis or its Affiliates in the Ionis Territory for the Licensed Products during
              the period from the date of such update until the next JSC meeting. Without limiting the foregoing, at Otsuka&#8217;s reasonable request, Ionis will provide to Otsuka, [***], all information relating to the [***].</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">18</font></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;" noshade="noshade"></div>
    </div>
    <table id="z21ec5f31f0814f268ea8aebfd0d3a1b8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Pricing</font>. All decisions for the Licensed Products related to list price, targeted net pricing, sales-weighted average discounts and rebates, pricing strategy (including the approach to pricing with
              different types of accounts and plans, including types of discounts and rebates), and modifications to any of the foregoing, will be made by (a) Ionis in the Ionis Territory and (b) Otsuka in the Otsuka Territory; <font style="font-style: italic;">provided </font>that, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z98b288d095e745d5bb03f8f196846584" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Global Brand Strategic and Operating Plan</font>. Ionis will develop, [***] a global brand strategic and operating plan with respect to the Commercialization of the Licensed Products throughout the
              Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Global Brand Strategic and Operating Plan</font>&#8221;). The Global Brand Strategic and Operating Plan shall at all times conform to applicable Professional Requirements and
              Applicable Law (including compliance requirements). Ionis, through the JSC, will update the Global Brand Strategic and Operating Plan [***]. In addition, [***], either Party may propose material updates or modifications to the Global Brand
              Strategic and Operating Plan to [***]. No update or modification to the Global Brand Strategic and Operating Plan will be effective unless and until [***]. Once [***], such updated version of the Global Brand Strategic and Operating Plan will
              automatically become effective and replace the then-prior version of the Global Brand Strategic and Operating Plan. The Global Brand Strategic and Operating Plan will include, in reasonable detail, the Trademarks to be used by the Parties or
              its Affiliates or its or their Sublicensees for the Commercialization of Licensed Product, trade dress, positioning, market access strategy, and marketing strategic imperatives, objectives and messaging with respect to the Licensed Products.<font style="font-style: italic;">&#160;</font>At Otsuka&#8217;s reasonable request, Ionis will provide to Otsuka, [***]. Ionis will, [***], lead and conduct all Commercialization activities for the Licensed Products in the Ionis Territory [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z0c005510d7fd498da90a4dbad0a1301e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka Territory Brand Strategic and Operating Plan</font>. Within [***] after [***] approves the initial Global Brand Strategic and Operating Plan, Otsuka will prepare and submit to [***] a brand strategic
              and operating plan with respect to the Commercialization of the Licensed Products in the Otsuka Territory (such plan, the &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Brand Strategic and Operating Plan</font>&#8221;).
              [***] will review, discuss and determine whether to approve the initial Otsuka Territory Brand Strategic and Operating Plan. The Otsuka Territory Brand Strategic and Operating Plan will, at all times during the Term, be consistent with the
              then-current Global Brand Strategic and Operating Plan, except to the extent such inconsistency is (a) necessary to (i) conform with any written requirement from any Regulatory Authority or with any Applicable Law or Professional Requirements
              in the Otsuka Territory or (ii) avoid infringement of a Third Party Trademark in the Otsuka Territory, or (b) approved by the JSC (by unanimous Party Vote). On [[***] during the Term (and more frequently as may be necessary), Otsuka will
              prepare an update to the Otsuka Territory Brand Strategic and Operating Plan. [***] will review, discuss and determine whether to approve each update to the Otsuka Territory Brand Strategic and Operating Plan. Once approved by [***], the
              Otsuka Territory Brand Strategic and Operating Plan will automatically become effective and, in the case of an update, will supersede the previous Otsuka Territory Brand Strategic and Operating Plan as of the date of such approval by [***].
              Otsuka will, at its cost and expense, lead and conduct all Commercialization activities in the Otsuka Territory [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z0476952ff3f1439c988f9e0666588b42" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka Commercialization Diligence Obligations</font>. On a country-by-country basis in the Otsuka Territory, following [***], Otsuka will use Commercially Reasonable Efforts to obtain Reimbursement
              Approval for and otherwise Commercialize such Licensed Product in such country.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z4bfe3a46ea594f3c898d05b6778f8050" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold; color: rgb(0, 0, 0);">Medical Affairs Plans</font><font style="color: rgb(0, 0, 0);">.</font></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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">19</font></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;" noshade="noshade"></div>
    </div>
    <table id="z4979d75cabb14d0489bc919672a00c0b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">6.7.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Global Medical Affairs Pla</font><font style="font-weight: bold; color: rgb(0, 0, 0);">n</font><font style="color: rgb(0, 0, 0);">. </font>Ionis will develop, and will [***], a plan for the global Medical
              Affairs activities for the Licensed Products throughout the Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Global Medical Affairs Plan</font>&#8221;). The Global Medical Affairs Plan shall at all times conform to applicable
              Professional Requirements and Applicable Law (including compliance requirements) with adjustments necessary to comply with local Applicable Law and Professional Requirements in the Otsuka Territory. Ionis, through the JSC, will update the
              Global Medical Affairs Plan on [***] basis. In addition, between [***] updates, either Party may propose material updates or modifications to the Global Medical Affairs Plan [***]. No update or modification to the Global Medical Affairs Plan
              will be effective unless and until approved by [***]. Once approved by [***], such updated version of the Global Medical Affairs Plan will become effective and replace the then-prior version of the Global Medical Affairs Plan. Ionis will, at
              its cost and expense, lead and conduct all Medical Affairs activities for the Licensed Products in the Ionis Territory [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="ze1b407c786204660a63bf97cbed237a6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">6.7.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka Territory Medical Affairs Plan</font><font style="color: rgb(0, 0, 0);">.</font><font style="font-weight: bold; font-style: italic;">&#160;</font>Within [***] after [***] approves the initial Global
              Medical Affairs Plan, Otsuka will prepare and submit to [***] a plan for the Medical Affairs activities for the Licensed Products in the Otsuka Territory (such plan, the &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory
                Medical Affairs Plan</font>&#8221;). [***] will review, discuss and determine whether to approve the initial Otsuka Territory Medical Affairs Plan. The Otsuka Territory Medical Affairs Plan will, at all times during the Term, be consistent with
              the then-current Global Medical Affairs Plan, except to the extent such inconsistency is (a) necessary to conform with any written requirement from any Regulatory Authority or with any Applicable Law or Professional Requirements in the Otsuka
              Territory or (b) approved by the JSC (by unanimous Party Vote). On [***] during the Term (and more frequently as may be necessary), Otsuka will prepare an update to the Otsuka Territory Medical Affairs Plan. [***] will review, discuss, and
              determine whether to approve each update to the Otsuka Territory Medical Affairs Plan. Once approved by [***], the Otsuka Territory Medical Affairs Plan will automatically become effective and, in the case of an update, supersede the previous
              Otsuka Territory Medical Affairs Plan as of the date of such approval by the JSC. Otsuka will, at its cost and expense, lead and conduct all Medical Affairs activities in the Otsuka Territory [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z62fd838631244d77b31b99e87f967bfa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Standards of Conduct; Compliance</font>. Each Party will perform, or will ensure that each of its Affiliates, Sublicensees, and Subcontractors perform, all Commercialization and Medical Affairs activities
              in a professional and ethical business manner and in compliance with Applicable Law and applicable Professional Requirements.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="ze097b05936a849caa95afd9a9fc2b1dc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Product Materials</font>. Each Party will, at its cost and expense, be responsible for preparing, developing, producing, or otherwise obtaining, and utilizing promotional materials, training materials,
              medical education materials, Packaging and Labeling, and all other literature or other information related to the Licensed Products (&#8220;<font style="font-weight: bold; font-style: italic;">Product Materials</font>&#8221;) to support its
              Commercialization and Medical Affairs activities in such Party&#8217;s Territory, which Product Materials will at all times [***]. From time to time, and in any event upon Otsuka&#8217;s request, Ionis will share with Otsuka samples of Product Materials
              Controlled by Ionis and which are used by Ionis, its Affiliates, or licensees in connection with the Commercialization of or conduct of Medical Affairs activities for the Licensed Products. From time to time, and in any event upon Ionis&#8217;
              request, Otsuka will share with Ionis samples of Product Materials Controlled by Otsuka and which are used by Otsuka, its Affiliates or sublicensees in connection with the Commercialization of or conduct of Medical Affairs activities the
              Licensed Products in the Otsuka Territory.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc98c43380385419a8a0c95de71c3922f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Diversion</font>. Neither Party nor its Affiliates will, and each Party will take reasonable measures to ensure that its Sublicensees, licensees, and Subcontractors do not, either directly or to such
              Party&#8217;s knowledge, intentionally indirectly,<font style="font-weight: bold; font-style: italic;">&#160;</font>promote, market, distribute, import, sell, or have sold any Licensed Product to any Third Party or to any address or Internet Protocol
              address or the like outside of such Party&#8217;s Territory including via the Internet or mail order. Notwithstanding any provision to the contrary set forth in this Agreement, [***]. As applicable, (i) in the case of Otsuka, in any country or
              jurisdiction outside of the Otsuka Territory, and (ii) in the case of Ionis, in any country or jurisdiction outside of the Ionis Territory:</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">20</font></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;" noshade="noshade"></div>
    </div>
    <table id="z23fc3de2f5264239af61834890a75c32" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">6.10.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>such Party and its Affiliates will not engage, nor permit its Sublicensees, licensees, and Subcontractors to engage, in any advertising or promotional activities relating to any Licensed Product for use directed primarily to customers or
              other buyers or users of the Licensed Products located in any such country or jurisdiction;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7509113b4fd54b37b11e2c27ae555f34" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">6.10.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>such Party and its Affiliates will not solicit orders of the Licensed Products from any prospective purchaser located in any such country or jurisdiction;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">6.10.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>such Party and its Affiliates will not, and will <font style="color: rgb(0, 0, 0);">take reasonable measures to </font>cause its Sublicensees, licensees and Subcontractors to not, deliver or tender (or cause to be delivered or tendered)
              any Licensed Product to Third Parties for use in such country or jurisdiction; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zdd984a09c76f4ff09225e296d46d6acd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">6.10.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>if either Party or its Affiliates, Sublicensees, or licensees receive any order for any Licensed Product from a prospective purchaser located in any such country or jurisdiction, then such Party will immediately refer that order to the
              other Party or its designee and will not accept any such orders.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 7</div>
    <div style="text-align: center; font-weight: bold;">MANUFACTURING</div>
    <div>&#160;</div>
    <table id="z7110fe71d463464e841c87e610b72f70" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Responsibility</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zbb491bfe1c7740eab42c07c3fec06e5a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">7.1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Manufacturing</font>. Ionis will have sole control over and decision-making authority with respect to, at its cost and expense, the Manufacture of (a) all supplies of the Licensed Products required
              for Ionis&#8217; activities under the Cross-Territory Clinical Development Plan and the Non-Clinical HAE Development Plan, and for all Development activities in the Ionis Territory and (b) all supplies of the Licensed Products for Commercialization
              purposes in the Ionis Territory. In addition, but subject to <u>Section 7.1.2</u> (Otsuka Manufacturing), in accordance with the Supply Agreements and Quality Agreements, Ionis will Manufacture and supply Otsuka with all Licensed Product
              that is necessary for Otsuka to (i) [***] and (ii) [***]. Upon Otsuka&#8217;s reasonable request prior to the Manufacturing Handover Date, Ionis will provide (or will use commercially reasonable efforts to cause its CMOs to provide) to Otsuka (A)
              [***], (B) [***], and (C) [***]. Ionis will provide all such Requested Assistance to Otsuka in accordance with the terms of <u>Section 3.2</u> (Technology Transfer Cost) and will provide such data and information to Otsuka [***]. For
              clarity, and notwithstanding anything to the contrary herein, Ionis will provide to the Qualified Person for the Licensed Products in the Otsuka Territory, [***], Manufacturing audit or inspection reports as required under EU GMP, Annex 16,
              section 2.2 for the purposes of batch certification in the Otsuka Territory.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">21</font></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;" noshade="noshade"></div>
    </div>
    <table id="zb43d49c649ac4b82a06c9d46a9096bdd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">7.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka Manufacturing</font>. Otsuka will have the right to assume responsibility for Manufacturing (a) all supplies of the Licensed Products required for Otsuka&#8217;s activities under the Otsuka
              Territory-Specific Development Plan and (b) all supplies of the Licensed Products for Commercialization purposes in the Otsuka Territory, in each case, upon written notice to Ionis at any time after the earliest of (i) [***], (ii) [***] and
              (iii) [***] (such notice, a &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Handover Notice</font>&#8221;). If Otsuka provides Ionis with a Manufacturing Handover Notice, then Ionis&#8217; obligations to Manufacture and supply Otsuka
              in accordance with <u>Section 7.1.1</u> (Ionis Manufacturing) will terminate, following the completion of all activities under the Manufacturing Technology Transfer Agreement in accordance with <u>Section 7.4</u> (Manufacturing Technology
              Transfer), and the initiation of actual Manufacturing of the Licensed Products to be sold by or on behalf of Otsuka at Otsuka&#8217;s or its designee&#8217;s manufacturing facility (such date, the &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing
                Handover Date</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z4d7b8367671a4346ba3a0c763c0877ff" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Supply and Quality Agreements; Manufacturing Costs</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z641cdacd92ff4c328dbbbac04d1e9882" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">7.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Clinical Supply Agreement</font>. Unless otherwise agreed by the Parties, within a timeframe following the Effective Date to be agreed by the Parties, the Parties will negotiate in good faith and enter into
              a supply agreement on reasonable and customary terms for the supply of Licensed Products by Ionis to Otsuka for clinical use (the &#8220;<font style="font-weight: bold; font-style: italic;">Clinical Supply Agreement</font>&#8221;), which agreement
              (together with the related Quality Agreement) will govern the terms and conditions of the Manufacture and supply of the Licensed Products for Development purposes in the Otsuka Territory. Otsuka will pay a supply price to Ionis under the
              Clinical Supply Agreement equal to [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zbd405ccd17634385a6af15c65e9556a7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">7.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Commercial Supply Agreement</font>. Within a timeframe following the Effective Date to be agreed by the Parties, the Parties will negotiate in good faith and enter into a commercial supply agreement on
              reasonable and customary terms for the commercial-grade supply of Licensed Products by Ionis to Otsuka (the &#8220;<font style="font-weight: bold; font-style: italic;">Commercial Supply Agreement</font>&#8221; and together with the Clinical Supply
              Agreement, the &#8220;<font style="font-weight: bold; font-style: italic;">Supply Agreements</font>&#8221;), which agreement (together with the related Quality Agreement) will govern the terms and conditions of the Manufacture and supply of the Licensed
              Products for Commercialization purposes in the Otsuka Territory. Otsuka will pay a supply price to Ionis under the Commercial Supply Agreement equal to [***]. The Commercial Supply Agreement shall allow Otsuka to order, and Ionis to supply, a
              portion of a batch as minimum order quantity, for a duration of at least [***], as further detailed in such Commercial Supply Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7690ac59465242e89ab0b139819545ef" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">7.2.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Quality Agreements</font>. The Parties will negotiate in good faith and enter into one or more quality technical agreements pertaining to clinical and commercial supply of Licensed Products to Otsuka (each,
              a &#8220;<font style="font-weight: bold; font-style: italic;">Quality Agreement</font>&#8221;) containing reasonable and customary terms and conditions regarding quality assurance, quality control, compliance with GMP, GDP and GCP (as applicable),
              specifications, change control procedures, and provisions relating to audits and inspections.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="ze3ceb378277d46679c20f818b6fb8d7c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">7.2.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Manufacturing Cost Increases</font>. If the Manufacturing Costs, whether for clinical or commercial supplies of Licensed Product, are reasonably anticipated to increase, on a per unit basis, such that the
              [***], then Ionis will provide prompt written notice to Otsuka of such increase. If such increase is anticipated to result in [***], on a per unit basis, then [***]. If such increase is anticipated to result in [***] on a per unit basis, then
              [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z0f036069eeb847a792a4b99656705eac" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">7.2.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Capital Expenditures</font>. Ionis [***]. In addition, if any CMO requests or requires [***], then Ionis will notify Otsuka and the Parties will [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z8c018c09d1714024b3108c1dcea5d5f8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">7.2.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***]. If the reasonable allocation of [***], then [[***].</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">22</font></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;" noshade="noshade"></div>
    </div>
    <table id="z52bb62fb45424f87a730f29adb86f9ba" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">&#160;Audits and Inspections</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zaf8d9103a4dd4278bd83698cf047e961" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">7.3.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">By Otsuka</font>. Prior to execution of the first Quality Agreement, Otsuka shall be entitled to conduct [***]. In addition, if Ionis elects to inspect or audit any facilities of its CMOs with respect to
              the Manufacture of Licensed Products for the Otsuka Territory, Ionis shall notify Otsuka of such inspection or audit and, [***]. In addition, to the extent permitted under Ionis&#8217; agreement with the applicable CMO and subject to any conditions
              set forth in such agreement with respect to any inspection or audit (e.g., an obligation to enter into a confidentiality agreement with the applicable CMO), Ionis shall [***]. If Otsuka identifies the need to perform a &#8220;for cause&#8221; audit of
              such facilities to address quality or compliance issues related to any Licensed Product Manufactured for the Otsuka Territory (including to address any notice from a Governmental Authority in the Otsuka Territory of noncompliance with
              Applicable Laws), as well as in connection with the preparation of Regulatory Submissions for the Otsuka Territory and in response to Regulatory Authority requirements in the Otsuka Territory, then Otsuka shall notify Ionis and if Ionis
              agrees with Otsuka&#8217;s determination that a &#8220;for cause&#8221; audit is needed, Ionis will schedule and conduct such audit and Otsuka will [***], in each case, to the extent permitted pursuant to the applicable agreement with the such CMO.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z10d1790764b54f4f95f247a19901dd79" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">7.3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">By Governmental Authority</font>. If any Governmental Authority carries out or gives notice of its intention to carry out any inspection or audit of any of Ionis&#8217; CMOs in relation to Manufacture of Licensed
              Products for the Otsuka Territory and Ionis is aware of such upcoming inspection or audit, then Ionis shall promptly notify Otsuka thereof and Ionis shall, to the extent permitted by its agreement with the applicable CMO and the applicable
              Governmental Authority, [***]. Following receipt by Ionis of the inspection results or audit observations of the Governmental Authority from such inspection or audit (a redacted copy of which Ionis will promptly provide to Otsuka to the
              extent it relates to Licensed Products Manufactured for the Otsuka Territory), Ionis will (a) prepare any appropriate responses and (b) provide a copy of such responses to Otsuka [***] in advance of the date such responses are due, to the
              extent such responses pertain to the Manufacture of Licensed Products for the Otsuka Territory, and Ionis shall [***], in each case ((a) and (b)), to the extent permitted under Ionis&#8217; agreement with such CMOs and subject to any conditions set
              forth in the applicable agreement with such CMOs with respect to any inspection or audit (e.g., an obligation to enter into a confidentiality agreement with the applicable CMO).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z37006a81692e41928efcdc3b337bd285" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">7.3.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">CMO Agreements</font>.<font style="font-weight: bold;">&#160;</font>Ionis shall [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zbe88194985bd49029cb265656648f444" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Manufacturing Technology Transfer</font>. At Otsuka&#8217;s request any time after Otsuka provides a Manufacturing Handover Notice, Ionis will make available to Otsuka all Ionis Manufacturing and Analytical
              Know-How and materials (the &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology Transfer</font>&#8221;). Otsuka will (a) use Ionis Manufacturing and Analytical Know-How and materials provided by Ionis in connection with
              the Manufacturing Technology Transfer only in the fulfillment of obligations or exercise of rights under this Agreement, and (b) not transfer such Ionis Manufacturing and Analytical Know-How or materials or deliver the same to any Third
              Party, without Ionis&#8217; prior written consent. For purposes of the Manufacturing Technology Transfer, the Parties together with Ionis&#8217; CMO (subject to the next sentence) will enter into a manufacturing technology transfer agreement, which will
              also provide for reasonable technical assistance and support by Ionis and Ionis&#8217; CMOs as reasonably requested by Otsuka to enable Otsuka or its Affiliates, or if agreed by Ionis, a Third Party manufacturer (other than Ionis&#8217; CMOs), to
              Manufacture the Licensed Products (&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology Transfer Agreement</font>&#8221;). Ionis will use reasonable efforts to [***]. If Ionis agrees to transfer Ionis Manufacturing and
              Analytical Know-How to a Third Party manufacturer other than Ionis&#8217; CMOs, such transfer shall be carried out pursuant to a direct license between Ionis and such Third Party manufacturer. If Otsuka [***]. Otsuka will [***]. Accordingly, Ionis
              may [***]. Each Party will [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">23</font></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;" noshade="noshade"></div>
    </div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 8</div>
    <div style="text-align: center; font-weight: bold;">GOVERNANCE</div>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Joint Steering Committee</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z1850078a77d34766a1d833289e9eb121" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Formation and Purpose of the JSC</font>. Promptly, but not more than [***] after the Effective Date, Ionis and Otsuka will establish a Joint Steering Committee (&#8220;<font style="font-weight: bold; font-style: italic;">JSC</font>&#8221;), which will have the responsibilities set forth in this <u>Article 8</u> (Governance) and will oversee, review, monitor, coordinate, and, where specified in this <u>Section 8.1</u> (Joint Steering Committee), approve
              the Parties&#8217; Development, Manufacturing, Medical Affairs, and Commercialization activities under this Agreement for the Licensed Products in the Territory in accordance with this <u>Section 8.1</u> (Joint Steering Committee). The JSC will
              dissolve upon the expiration of the Term.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Membership</font>. The JSC will be composed of an equal number of representatives from each Party who have the appropriate and direct knowledge and expertise and requisite decision-making authority. Any
              such representative who serves on the JSC or any committee under this Agreement may also serve on one or more other committees under this Agreement. Each Party may replace any of its representatives on the JSC and appoint a person to fill the
              vacancy arising from each such replacement. A Party that replaces a representative will notify the other Party at least [***] prior to the next scheduled meeting of the JSC. Ionis will designate one of its JSC members as one of the
              co-chairpersons of the JSC and Otsuka will designate one of its members as the other co-chairperson of the JSC (each, a &#8220;<font style="font-weight: bold; font-style: italic;">JSC</font><font style="font-style: italic;">&#160;</font><font style="font-weight: bold; font-style: italic;">Co-Chairperson</font>&#8221;). The JSC Co-Chairpersons or their designees, in collaboration with the Alliance Managers, will be responsible for calling meetings, preparing and circulating an agenda
              and related information in advance of each meeting, and preparing and issuing minutes of each meeting within [***] thereafter. Such minutes will not be finalized until the JSC Co-Chairpersons or their designees have had [***] to review and
              confirm the accuracy of such minutes.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z85db70fda0cd4660aec347d19a016767" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Meetings</font>. The JSC will hold meetings at such times as it elects to do so, but will meet no less frequently than quarterly prior to [***] and thereafter no less frequently than [***], in each case,
              unless otherwise agreed by the Parties. The JSC may meet in person or by means of teleconference, Internet conference, video conference, or other similar communication method. Each Party will be responsible for all of its own costs and
              expenses of participating in any JSC meeting.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.1.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Meeting Agendas</font>. Unless agreed otherwise by the Parties, the Parties will jointly prepare the agenda for each JSC meeting, facilitated by the Alliance Managers working closely with the JSC
              Co-Chairpersons and, as appropriate, other JSC members and Subcommittee co-chairpersons, at least [***] in advance of each meeting of the JSC, and each Party will provide the other Party with all relevant materials to be presented at each JSC
              meeting at least [***] in advance of each meeting of the JSC; <font style="font-style: italic;">provided</font> that under exigent circumstances requiring JSC input, the agenda may be prepared or presentation materials may be provided within
              a shorter period of time in advance of a meeting, with the approval of the JSC Co-Chairpersons. Either Party may propose that there not be a specific agenda for a particular meeting, so long as the other Party consents to the later addition
              or modification of agenda items or the absence of a specific agenda for such JSC meeting.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">24</font></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;" noshade="noshade"></div>
    </div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.1.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <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 id="zf7d5782bdf12420eaea73396cebf3a09" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
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          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>manage the overall strategic alignment between the Parties under this Agreement and maintain the relationship between the Parties;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7fa7c7fe3d09429ea6a1e78848cad6f7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss, and determine whether to [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z0c2e174a54294648976498a377d3601b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss, and determine whether [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc95cc6c8a1bf4cba95221737a9104ec2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss, and determine whether [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd3cfe709c519468b9c6751c9aee446b1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(e)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss, and determine whether [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss and determine whether [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zde059b0132224988bff85249548180d4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(g)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss, and determine whether to approve any updates to the Shared Development Budget, as described in <u>Section 4.4.2(a)</u> (Shared Development Budget);</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zcfdb5ee9238f4bbdbd605825a9be21f8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
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          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss, and determine whether to approve [***] and the Shared Development Budget, as described in <u>Section 4.4.4(a)</u> (Shared Costs);</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z6d08765a96754e3bbe1c7f551975402e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>share information related to, and review and discuss activities and progress of each Party in connection with the Development of Licensed Products in its Territory, including activities and progress under the Cross-Territory Clinical
              Development Plan, Non-Clinical HAE Development Plan, and the Otsuka Territory-Specific Development Plan, including through updates from each Party of the status of Development for the Licensed Products in each Party&#8217;s Territory, as described
              in <u>Section 4.5</u> (Development Reports);</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z6814f06669ed49fd96d5e727b9edb4bc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review and discuss any matters related to the Development of the Licensed Products referred to the JSC by either Party&#8217;s representatives;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zb3879d4ee2cf40d08c8a53d9e6ddac23" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(k)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>discuss any concerns raised by either Party regarding any action that the other Party is taking or intends to take with respect to a Licensed Product that is [***], as described in <u>Section 5.8</u> (No Harmful Actions);</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zfc84cdefb2ce4f919dbd4bded74f74a5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(l)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>discuss [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="za2513b3376744b1d904dc463027b7179" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(m)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss, and determine whether to approve [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc64c0940ae7c40af9f779b1d77e11198" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(n)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss, and determine whether to approve [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zbeb26feaa2234951beb3eee424034d1c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(o)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss, and determine whether to approve [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd5139904a275454b813d5478ad15a79f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(p)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss and determine whether to approve [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="za292fd7fe40f4b0ea2495186b029e0ee" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(q)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review and discuss any matters related to the Commercialization of the Licensed Products referred to the JSC by either Party&#8217;s representatives;</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">25</font></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;" noshade="noshade"></div>
    </div>
    <table id="z125cba459ff144d4b588908aa98516fe" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(r)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>discuss the inclusion of Ionis&#8217; logo, name, and housemark on the packaging for the Licensed Products in the Otsuka Territory, as described in <u>Section 10.10.6</u> (Housemarks);</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z14590c8d69bd4bcd829361202513d8ff" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(s)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>establish and delegate specifically defined duties to any Subcommittees, as described in <u>Section 8.2.1</u> (Formation; Authority);</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z0dbf755ca2f349178f13940e78705868" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(t)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>attempt to resolve any disputes or disagreements arising from matters within the jurisdiction of any Subcommittee; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z40a41c5c38174ac0b2819f2e9114e789" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(u)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>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 id="za2786bdf0b4249eb830a897d2be01fce" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Additional Committees</font><u>.</u></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z6d4d422acb1e44449b8135340a54d5d7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Formation; Authority</font>. In addition to the Regulatory Subcommittee and the PV Subcommittee, the JSC may establish and delegate specifically-defined duties to operational committees or <font style="font-style: italic;">ad hoc</font> subcommittees, on an &#8220;as needed&#8221; basis to oversee particular projects or activities (any such operational committees and subcommittees, including the Regulatory Subcommittee, a &#8220;<font style="font-weight: bold; font-style: italic;">Subcommittee</font>&#8221;). Each such Subcommittee will be constituted and will operate as the JSC determines. Each Subcommittee and its activities will be subject to the oversight of, and will
              report to, the JSC. The JSC or the JSC Co-Chairpersons, in each case as mutually agreed, may delegate to a Subcommittee any responsibilities of the JSC set forth in <u>Section 8.1.5</u> (Specific Responsibilities of the JSC), and, in such
              case, any agreement reached by unanimous Party Vote of the applicable Subcommittee with respect to such delegated responsibilities will be deemed to be approved by the JSC (to the extent such approval is required hereunder). The JSC or the
              JSC Co-Chairpersons acting together may also reallocate any responsibility of a Subcommittee to any other Subcommittee. No Subcommittee&#8217;s authority may exceed that specified for the JSC in this <u>Article 8</u> (Governance). Any disagreement
              between the representatives of the Parties on a Subcommittee will be referred to the JSC for resolution in accordance with <u>Section 8.4</u> (Decision-Making).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zf531c9e8279e43e687917075a020a315" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Subcommittee Leadership and Meetings</font>. Ionis will designate a co-chairperson of each Subcommittee and Otsuka will designate a co-chairperson of each Subcommittee, each of whom will be a Party&#8217;s
              representative who is a member of such Subcommittee (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Subcommittee</font><font style="font-style: italic;">&#160;</font><font style="font-weight: bold; font-style: italic;">Co-Chairperson</font>&#8221;).
              The Subcommittee Co-Chairpersons or their designees, 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 promptly thereafter. Such minutes will not be finalized until all Subcommittee members have had [***] to review and confirm the accuracy of such minutes. Each Party may replace its representatives and Subcommittee Co-Chairpersons
              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 will hold
              meetings at such times as it elects to do so, and at such locations as the Parties may agree upon or by means of teleconference, Internet conference, video conference, or other similar communication method. Each Party will be responsible for
              all of its own expenses of participating in any Subcommittee meeting.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">26</font></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;" noshade="noshade"></div>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Additional Participants</font>. Employees of a Party or any of its Affiliates involved in the Exploitation of the Licensed Products may attend meetings of the JSC or any Subcommittee as non-voting
              participants. In addition, with the prior consent of each Party, consultants, representatives, or advisors involved in the same activities and 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 12</u> (Confidentiality) may attend meetings of the JSC or any Subcommittee as non-voting observers.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Decision-Making</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.4.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">General Decision-Making Process</font>. Each Party&#8217;s representatives on the JSC and each Subcommittee will, collectively, have one vote (the &#8220;<font style="font-weight: bold; font-style: italic;">Party Vote</font>&#8221;)
              on all matters brought before such committee for a decision by consensus. The JSC and each Subcommittee will make decisions as to matters within its jurisdiction by unanimous Party Vote, which may be reflected in the minutes of the committee
              meeting or by an action by written consent signed by the JSC Co-Chairpersons or their designees identified in writing. Except as otherwise expressly set forth in this Agreement, the phrase &#8220;determine,&#8221; &#8220;designate,&#8221; &#8220;approve,&#8221; or &#8220;determine
              whether to approve&#8221; by the JSC or any Subcommittee and similar phrases used in this Agreement will mean approval in accordance with this <u>Section 8.4</u> (Decision&#8209;Making), including the escalation and tie&#8209;breaking provisions herein. For
              the avoidance of doubt, matters that are specified in <u>Section 8.1.5</u> (Specific Responsibilities of the JSC) 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 8.4</u> (Decision&#8209;Making) or <u>Section 8.5</u> (Resolution of Committee Disputes).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.4.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Decisions of the Subcommittees</font>. If any Subcommittee cannot reach unanimous agreement using good faith efforts on any matter within their respective scope of authority within [***] of the meeting at
              which such matter was discussed, then a Party may refer such matter to the JSC for resolution in accordance with <u>Section 8.4.3</u> (Decisions of the JSC).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zfba383f6dd02462a8c8f119597933b17" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.4.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Decisions of the JSC</font>. The JSC will use good faith efforts, in compliance with this <u>Section 8.4.3</u> (Decisions of the JSC), to promptly resolve any such matter for which it has authority. If,
              after the use of good faith efforts, including reasonable discussion and good faith consideration of each Party&#8217;s view on a particular matter, the JSC is unable to resolve any such matter referred to it by any Subcommittee or any matter with
              respect to the matters within the scope of the JSC&#8217;s authority, in each case, within a period of [***], then either Party may refer such matter to the Party&#8217;s respective Executive Officer for resolution in accordance with <u>Section 8.5.1</u>
              (Referral to Executive Officers).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z41df2f2685f84c6db0c268c50b962817" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Resolution of Committee Disputes</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.5.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Referral to Executive Officers</font>. If a Party makes an election under <u>Section 8.4.3</u> (Decisions of the JSC) to refer for resolution by the Executive Officers a matter as to which the JSC cannot
              reach a consensus decision, then the JSC will submit in writing the respective positions of the Parties to their respective Executive Officers. The Executive Officers will use good faith efforts to resolve any such matter so referred to them
              as soon as practicable but, in any event, within [***] after such matter is referred to them (or such longer period as the Executive Officers may agree upon), and any final decision that the Executive Officers agree to in writing will be
              conclusive and binding on the Parties.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">27</font></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;" noshade="noshade"></div>
    </div>
    <table id="zf81d1e6faa5f4ae7ad7673c43a0174c0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.5.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Final Decision-Making Authority</font>. If the Executive Officers are unable to reach agreement on any such matter so referred within [***] after such matter is referred to them (or such longer period as
              the Executive Officers may agree upon), then, subject to <u>Section 8.5.3</u> (Limitations on Decision Making):</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
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          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Change; Status Quo</font>. Neither Party will have final decision-making authority with respect to the final resolution of any disagreement related to: (i) [***]; (ii) [***]; (iii) [***]; (iv) [***]; (v)
              [***]; and (vi) [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zfc1db0c87f774247b2a873ffee5528ae" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Final Decision-Making Authority</font>. Ionis will have final decision-making authority over (i) [***], (ii) [***], (iii) [***], (iv)&#160; [***], and (vi) [***]. Notwithstanding the foregoing, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7b4f664072a74bdaa89d9c64bd3288e2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka Final Decision-Making Authority</font>.<font style="font-weight: bold; font-style: italic;">&#160;</font>Otsuka will have final decision making authority over (i) [***], (ii) [***], (iii) [***], and (iv)
              [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zdd33a3e7ff6a4e5baad5a379494ad23c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">8.5.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Limitations on Decision Making</font>. Notwithstanding anything to the contrary set forth in this Agreement, without the other Party&#8217;s prior written consent, no decision of the JSC, any Subcommittee, or a
              Party&#8217;s Executive Officer (in the exercise of a Party&#8217;s decision&#8209;making authority on any such matters), in each case may, without the other Party&#8217;s prior written consent, (a) be likely to [***], (b) impose any requirements that the other
              Party take or decline to take any action that a Party reasonably believes would result in a violation of any Applicable Law, the requirements of any Regulatory Authority, or any agreement with any Third Party (including any Collaboration
              In-License) or the infringement or misappropriation of intellectual property rights of any Third Party, or (c) conflict with, amend, interpret, modify, or waive compliance under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z0f6f064d78364617a7d751415ba42987" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Day-to-Day Responsibilities</font>. Each Party will: (a) be responsible for day-to-day implementation and conduct of the activities hereunder for which it has or is otherwise assigned responsibility under
              this Agreement, <font style="font-style: italic;">provided</font> that such implementation is consistent with the express terms of this Agreement or the decisions of the JSC within the scope of its authority as provided herein; and (b)
              provide the other Party with information about material events related to the progress of such activities, as may be reasonably requested by the other Party from time to time.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z80f3d06565854ea8ac8f95287fb3b749" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Alliance Managers</font>. Each of the Parties will appoint a representative of such Party to act as its alliance manager under this Agreement no later than [***] after the Effective Date (each, an &#8220;<font style="font-weight: bold; font-style: italic;">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 all JSC meetings and the Alliance Managers or their respective designees will attend all Subcommittee meetings and will support the JSC Co-Chairpersons and any Subcommittee Co-Chairpersons in the discharge of their
              responsibilities. Alliance Managers will be non-voting participants in all JSC and Subcommittee meetings, but an Alliance Manager may bring any matter to the attention of the JSC or any Subcommittee if such Alliance Manager reasonably
              believes that such matter warrants such attention. 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 will 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; (d) plan and coordinate cooperative efforts and internal and external communications; and (e) take
              responsibility for ensuring that governance activities, such as the conduct of required JSC and any Subcommittee meetings and production of meeting minutes, occur as set forth in this Agreement, and that the relevant action items resulting
              from such meetings are appropriately carried out or otherwise addressed.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">28</font></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;" noshade="noshade"></div>
    </div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 9</div>
    <div style="text-align: center; font-weight: bold;">PAYMENTS</div>
    <div>&#160;</div>
    <table id="z81c06c09d04749ad8d727f6b08f62b94" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Upfront Payment</font>. Following the Effective Date, within [***], Otsuka will pay to Ionis, by wire transfer of immediately available funds, a non-refundable, non-creditable upfront payment of $65,000,000
              (the &#8220;<font style="font-weight: bold; font-style: italic;">Upfront Payment</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z019f5e77452b43bc9d4e2fef079df2a6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Milestone Payments</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z39f2ed87057b4be2b0ef644bb39f2f04" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">9.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Regulatory Milestones</font>. Subject to <u>Section 9.2.1(a)</u> (Regulatory Milestone Adjustment), after the first achievement of each regulatory milestone event set forth in Table 9.2.1 below by Otsuka
              or its Affiliates or Sublicensees for the first Licensed Product, Otsuka will pay to Ionis the corresponding regulatory milestone payment set forth in Table 9.2.1 (the regulatory milestone events set forth in Table 9.2.1, the &#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Milestone Events</font>&#8221; and the regulatory milestone payments set forth in Table 9.2.1, the &#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Milestone Payments</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="margin-left: 72pt;">
      <table id="zbe916bb2ddb94b208dfa4bd59923c314" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" border="0" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 1%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="vertical-align: top; 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 9.2.1 &#8211;Regulatory Milestones</div>
            </td>
          </tr>
          <tr>
            <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 68%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-style: italic; font-weight: bold;">Regulatory Milestone Event</div>
            </td>
            <td style="width: 30.68%; 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; font-style: italic; font-weight: bold;">Regulatory Milestone </div>
              <div style="text-align: center; font-style: italic; font-weight: bold;">Payment (in U.S. </div>
              <div style="text-align: center; font-style: italic; font-weight: bold;">Dollars)</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: 68%; 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 style="text-align: justify;">1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;[***]</div>
            </td>
            <td style="width: 30.68%; vertical-align: middle; 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;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 68%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify;">2.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;[***]</div>
            </td>
            <td style="width: 30.68%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</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: 68%; 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 style="text-align: justify;">3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;[***]</div>
            </td>
            <td style="width: 30.68%; vertical-align: middle; 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>

      </table>
    </div>
    <div><br>
    </div>
    <table id="ze152acb6b67b43b995007713410bae20" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Regulatory Milestone Adjustment</font>. If any [***], then the Regulatory Milestone Payments will be [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7720595df78c4b5f85425cccd727f913" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Notice and Payment</font>. Otsuka will notify Ionis in writing of the achievement of each Regulatory Milestone Event within [***] after achievement of such Regulatory Milestone Event by Otsuka or its
              Affiliates or within [***] after Otsuka&#8217;s receipt of notification of such achievement by its Sublicensees. However, in no event will a failure or delay by Otsuka<font style="font-weight: bold; font-style: italic;">&#160;</font>to deliver such
              notice of achievement of a Regulatory Milestone Event relieve Otsuka of its obligation to pay Ionis the corresponding Regulatory Milestone Payment for achievement of such Regulatory Milestone Event. Following receipt of such notice, Ionis
              will send Otsuka an invoice (and, if there has been any change to a Payment Form previously submitted, or if a previously submitted Payment Form has expired, then an updated Payment Form) for the applicable Regulatory Milestone Payment, and
              Otsuka shall pay such Regulatory Milestone Payment within [***] after receipt of such invoice (and Payment Forms, if applicable). Each Regulatory Milestone Payment<font style="font-weight: bold;">&#160;</font>is payable only once, regardless of
              the number of times the corresponding Regulatory Milestone Event is achieved. If Otsuka or its Affiliates or Sublicensees achieve all of the Regulatory Milestone Events, then the Regulatory Milestone Payments payable by Otsuka under this <u>Section
                9.2.1</u> (Regulatory Milestones) 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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">29</font></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;" noshade="noshade"></div>
    </div>
    <table id="z8760667b7c3a4a0fbb5770055f51605d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">9.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Sales Milestones</font>. After each sales milestone event set forth in Table 9.2.2 below is achieved by Otsuka or its Affiliates or Sublicensees for the Licensed Products in the Otsuka Territory, Otsuka
              will pay to Ionis the corresponding sales milestone payment, as set forth below (the sales milestone events set forth in Table 9.2.2, the &#8220;<font style="font-weight: bold; font-style: italic;">Sales Milestone Events</font>&#8221; and the sales
              milestone payments set forth in Table 9.2.2, the &#8220;<font style="font-weight: bold; font-style: italic;">Sales Milestone Payments</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="margin-left: 72pt;">
      <table id="za7c4cf2196f844ce9b327cf188cd09c0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" border="0" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 1%; vertical-align: top; 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; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" colspan="2">
              <div style="text-align: center; font-weight: bold;">Table 9.2.2 &#8211; Sales Milestones</div>
            </td>
          </tr>
          <tr>
            <td style="width: 1%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 75%; vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-style: italic; font-weight: bold;">Sales Milestone Event</div>
            </td>
            <td style="width: 23.86%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-style: italic; font-weight: bold;">Sales Milestone </div>
              <div style="text-align: center; font-style: italic; font-weight: bold;">Payment</div>
              <div style="text-align: center; font-style: italic; font-weight: bold;">(in U.S. Dollars)</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: 75%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-right: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify;">First Calendar Year in which the aggregate annual Net Sales of the Licensed Products in the Otsuka Territory equal or exceed [***]</div>
            </td>
            <td style="width: 23.86%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-right: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 75%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify;">First Calendar Year in which the aggregate annual Net Sales of the Licensed Products in the Otsuka Territory equal or exceed [***]</div>
            </td>
            <td style="width: 23.86%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</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: 75%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-right: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify;">First Calendar Year in which the aggregate annual Net Sales of the Licensed Products in the Otsuka Territory equal or exceed [***]</div>
            </td>
            <td style="width: 23.86%; 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); border-right: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">$[***]</div>
            </td>
          </tr>

      </table>
    </div>
    <div><br>
    </div>
    <table id="ze8fb835645f3419490122e222ec259ba" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Notice and Payment</font>. Otsuka will notify Ionis in writing of the achievement of each Sales Milestone Event no later than (i) [***] or (ii) [***]. However, in no event will a failure or delay by Otsuka<font style="font-weight: bold; font-style: italic;">&#160;</font>to deliver such notice of achievement of a Sales Milestone Event relieve Otsuka of its obligation to pay Ionis the corresponding Sales Milestone Payment for achievement of such Sale
              Milestone Event. Following receipt of such notice, Ionis will send Otsuka an invoice (and, if there has been any change to a Payment Form previously submitted, or if a previously submitted Payment Form has expired, then an updated Payment
              Form) for the applicable Sales Milestone Payment, and Otsuka shall pay such Sales Milestone Payment within [***] after receipt of such invoice (and Payment Forms, if applicable). If more than one of the Sales Milestone Events is achieved for
              the first time in a given Calendar Quarter during the Term, then Otsuka will pay to Ionis a separate Sales Milestone Payment with respect to each such Sales Milestone Event. Each Sales Milestone Payment<font style="font-weight: bold;">&#160;</font>is
              payable only once, regardless of the number of times the corresponding Sales Milestone Event is achieved. If Otsuka or its Affiliates or Sublicensees achieve all of the Sales Milestone Events, then the Sales Milestone Payments payable by
              Otsuka under this <u>Section 9.2.2</u> (Sales Milestones) will not exceed $[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z6cfe8d25499549dfb8ad3426c914ae18" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalties</font><font style="color: rgb(0, 0, 0);">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5bf49c59cc5a47d7a160738529b4faa6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">9.3.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Payments During the Initial Royalty Term</font>. Subject to the provisions of <u>Section 9.3.2</u> (Royalty Reductions), Otsuka will pay to Ionis royalties based on the Net Sales of a Licensed
              Product by Otsuka and its Affiliates and Sublicensees in the Otsuka Territory at the rates set forth in Table 9.3.1 below (the &#8220;<font style="font-weight: bold; font-style: italic;">Initial Royalties</font>&#8221;), on a Licensed Product-by-Licensed
              Product and country-by-country basis, commencing on the first sale of such Licensed Product that results in Net Sales of such Licensed Product in such country and ending on the latest to occur of (a) the [***] anniversary of the First
              Commercial Sale of such Licensed Product in such country, (b) the expiration of the last Valid Claim in the [***] that Cover such Licensed Product in such country [***], and (c) loss of Regulatory Exclusivity of such Licensed Product in such
              country (the &#8220;<font style="font-weight: bold; font-style: italic;">Initial Royalty Term</font>&#8221;).</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">30</font></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;" noshade="noshade"></div>
    </div>
    <div style="margin-left: 72pt;">
      <table id="z09e49ca6799e46bb999e756751efb302" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" cellpadding="0" cellspacing="0">

          <tr>
            <td style="width: 0.94%; vertical-align: middle; 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: middle; 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 9.3.1&#8211; Royalty Rates for the Licensed Products</div>
            </td>
          </tr>
          <tr>
            <td style="width: 0.94%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 83.71%; vertical-align: middle; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center; font-style: italic; font-weight: bold;">Calendar Year Net Sales of all Licensed Products in the Otsuka </div>
              <div style="text-align: center; font-style: italic; font-weight: bold;">Territory</div>
            </td>
            <td style="width: 15.07%; vertical-align: middle; 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-style: italic; font-weight: bold;">Royalty </div>
              <div style="text-align: center; font-style: italic; font-weight: bold;">Rate</div>
            </td>
          </tr>
          <tr>
            <td style="width: 0.94%; 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: 83.71%; 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 style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in the Otsuka Territory that is [***]</div>
            </td>
            <td style="width: 15.07%; 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: 0.94%; 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: 83.71%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in the Otsuka Territory that are [***]</div>
            </td>
            <td style="width: 15.07%; 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: 0.94%; 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: 83.71%; 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 style="text-align: justify;">Portion of annual Net Sales of all Licensed Products in the Otsuka Territory that are [***]</div>
            </td>
            <td style="width: 15.07%; 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>

      </table>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; margin-left: 36pt;">By way of example only, if Otsuka receives [***] in Net Sales of all Licensed Products during a given Calendar Year in the Otsuka Territory, then Otsuka would owe Ionis a royalty of [***] (as
      converted into U.S. Dollars in accordance with <u>Section 9.8</u> (Method of Payment; Exchange Rate)).</div>
    <div>&#160;</div>
    <table id="z4d59ff2ed49741b682d6a79524ab2547" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">9.3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Reductions</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z4b88e11479644023bd5b26caac33133a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Generic Approval</font>. On a country-by-country and Licensed Product-by-Licensed Product basis, if at any time during the Initial Royalty Term a Generic Product receives Regulatory Approval in a country in
              the Otsuka Territory, then, subject to <u>Section 9.3.2(e)</u> (Royalty Reductions Floor), the royalty rates set forth in Table 9.3.1 will be reduced by [***] for such Licensed Product in such country.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z816d3221dacf4bfa90dfbd3053555311" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Third Party Payments</font>. Subject to <u>Section </u><u>9.3.2(e)</u> (Royalty Reductions Floor), Otsuka may credit [***] of [***] in a country in the Otsuka Territory in a Calendar Quarter during the
              Royalty Term against the Royalties due and payable by Otsuka to Ionis on the Net Sales for such Licensed Product in such country in such Calendar Quarter; <font style="font-style: italic;">provided </font>that<font style="font-style: italic;">&#160;</font>the terms of this <u>Section </u><u>9.3.2(b)</u> (Third Party Payments) will not apply to any license agreement entered into without Ionis&#8217; prior written consent in violation of the terms of <u>Section 10.5.3</u>
              (Settlement). For clarity, Otsuka will not have the right to offset any Third Party Payments arising out of, or allocable to, the Manufacture of a Licensed Product.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z9568c3ee62f043c6a61dac1833ef4ba4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***]. Subject to <u>Section 9.3.2(e)</u> (Royalty Reductions Floor), on a Licensed Product-by-Licensed Product and country-by-country basis, if during any Calendar Quarter during the Initial Royalty Term for such Licensed Product in such
              country, (i) [***], and (ii) [***], then, commencing [***];<font style="font-style: italic;"> provided </font>that, if [***], then [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zaa36d40b6bef4d498286c0996393c72a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***]. Subject to <u>Section 9.3.2(e)</u> (Royalty Reductions Floor), on a Licensed Product-by-Licensed Product and country-by-country basis, during the Initial Royalty Term for such Licensed Product in such country, if, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="za9a6adb814fc423fa142f8bb68de2a90" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(e)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Reductions Floor</font>. In no event will the Royalties due to Ionis for a Licensed Product in a country in the Otsuka Territory [***] set forth in this <u>Section </u><u>9.3.2</u> (Royalty
              Reductions). Notwithstanding the foregoing, [***].</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">31</font></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;" noshade="noshade"></div>
    </div>
    <table id="z88290a6468694a1aa4318d55278d4c0f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">9.3.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Reduced Royalty Term</font>. On a Licensed Product-by-Licensed Product and country-by-country basis in the Otsuka Territory, following expiration of the Initial Royalty Term for a Licensed Product in a
              given country in the Otsuka Territory, Otsuka will pay Ionis a [***] royalty on the Net Sales of such Licensed Product by Otsuka and its Affiliates and Sublicensees in such country (the &#8220;<font style="font-weight: bold; font-style: italic;">Reduced
                Royalties</font>&#8221; and together with the Initial Royalties, the &#8220;<font style="font-weight: bold; font-style: italic;">Royalties</font>&#8221;) until the later of (a) [***], and (b) [***] (the &#8220;<font style="font-weight: bold; font-style: italic;">Reduced
                Royalty Term</font>&#8221; and together with the Initial Royalty Term, the &#8220;<font style="font-weight: bold; font-style: italic;">Royalty Term</font>&#8221;). For clarity, on a Licensed Product-by-Licensed Product and country-by-country basis, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zea98f545b4854b289cfb86241f3f311c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">9.3.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Payments and Reports</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z2d0bc8f7fd8b4be88abe1f1f2d53a954" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***]. Commencing with the Calendar Quarter during which the first sale of a Licensed Product is made that results in Net Sales anywhere in the Otsuka Territory, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="ze997dc3ebf1c4af2a86d2739dc0b0c4a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Report</font>. Commencing with the Calendar Quarter during which the first sale of a Licensed Product is made that results in Net Sales anywhere in the Otsuka Territory, within [***] after the end
              of each Calendar Quarter, Otsuka will provide to Ionis a written report (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Royalty Report</font>&#8221;) setting forth in reasonable detail: (i) the gross sales of the Licensed Products
              sold by Otsuka or its Affiliate or Sublicensee in the Otsuka Territory in such Calendar Quarter; (ii) the aggregate Net Sales of the Licensed Products sold by Otsuka or its Affiliates or Sublicensees in the Otsuka Territory in such Calendar
              Quarter; (iii) all deductions and reductions used to determine the Net Sales of the Licensed Products for such Calendar Quarter or the Royalties payable with respect to the Licensed Products for such Calendar Quarter, including any reduction
              pursuant to <u>Section 9.3.2</u> (Royalty Reductions) (if applicable); (iv) the exchange rates used to calculate the Royalties payable in U.S. Dollars; (v) any withholding taxes required to be made from such Royalties; and (vi) the quantity
              and description of the Licensed Products sold by Otsuka or its Affiliate or Sublicensee in the Otsuka Territory during such Calendar Quarter comprising such Net Sales. The Parties will seek to resolve any questions or issues related to a
              Royalty Report within [***] following receipt by Ionis of each Royalty Report.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zf99dfc26ea974f039edea2bbb26f925d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Payments</font>. The information contained in each Royalty Report will be considered the Confidential Information of Otsuka. Following receipt of each Royalty Report, Ionis will [***] and, [***],
              Otsuka will pay the Royalties due hereunder for the Calendar Quarter covered by the applicable Royalty Report.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="za300409d70e74ea8923eccbac4527624" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Other Amounts Payable</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 specified hereunder, within [***] after
              the end of each Calendar Quarter, each Party will provide an invoice, together with reasonable supporting documentation, to the other Party for such amounts owed in respect of such Calendar Quarter. The owing Party will pay any undisputed
              invoiced amounts within [***] after the date of the invoice, and any disputed amounts owed by a Party will be paid within [***] following resolution of the dispute.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">32</font></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;" noshade="noshade"></div>
    </div>
    <table id="z97b7c125d76445a4ad6910b21e0ab4a6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Financial Records and Audits</font>. Each Party will, and will require its Sublicensees and Subcontractors to, maintain complete and accurate records in accordance with such Party&#8217;s Accounting Standards in
              sufficient detail to permit the other Party to confirm the accuracy of any amounts payable under this Agreement for at least the preceding [***], including (as applicable) any Eligible Cross-Territory Development Costs, Milestone Payments,
              Royalties, and sales of the Licensed Products (including all calculations of Net Sales). Upon reasonable prior notice, each Party agrees to permit such records to be open during regular business hours for examination by an independent
              certified public accountant selected by the auditing Party and reasonably acceptable to the audited Party for the sole purpose of verifying the accuracy of the financial reports furnished by the audited Party pursuant to this Agreement or of
              any payments made, or required to be made, by the audited Party pursuant to this Agreement; <font style="font-style: italic;">provided </font>that<font style="font-style: italic;">&#160;</font>such independent accounting firm is subject to
              written obligations of confidentiality and non-use applicable to each Party&#8217;s Confidential Information that are at least as stringent as those set forth in <u>Article 12</u> (Confidentiality). Such audit will not be (a) performed more
              frequently than [***], or (b) repeated for any Calendar Year or with respect to the same set of records (in each case, except for cause). Such auditor will not disclose the audited Party&#8217;s Confidential Information to the auditing Party or to
              any Third Party, except to the extent such disclosure is necessary to verify the accuracy of the financial reports furnished by the audited Party or the amount of payments by the audited Party under this Agreement. The audited Party will pay
              any amounts shown to be owed to the auditing Party but unpaid within [***] after the accountant&#8217;s report, <font style="font-style: italic;">plus</font> interest (as set forth in <u>Section 9.11</u> (Late Payments; Disputed Payments)) from
              the original due date solely if the audited Party is responsible for the discrepancy. If such examination of records reveals any overpayment by Ionis, then Otsuka will reimburse Ionis for the amount overpaid within [***] after the
              accountant&#8217;s report, <font style="font-style: italic;">plus</font> interest (as set forth in <u>Section 9.11</u> (Late Payments; Disputed Payments)) from the original due date [***]. If such examination of records reveals any overpayment by
              Otsuka, then [***]. The auditing Party will bear the full cost of such audit unless such audit reveals an underpayment by the audited Party of more than [***] of the amount actually due for the time period being audited, in which case the
              audited Party will reimburse the auditing Party for the reasonable audit fees for such examination.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7874ead085a74a048ac222481dc889bb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Refunds</font>. Except as expressly provided herein, all payments under this Agreement will be irrevocable, non-refundable, and non-creditable.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc0b9cf4522544051a57f087ce395bc00" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Accounting Standards</font>. If a Party changes its general accounting principles from its then-current Accounting Standard (<font style="font-style: italic;">e.g.</font>, from GAAP to IFRS) at any time
              during the Term, then at least [***] prior to adopting such change in principles, such Party will provide written notice to the other Party of such change. A Party may not change its general accounting principles to any accounting standard
              other than GAAP or IFRS without the prior written approval of the other Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z8d32c37d4d804e818f6963efbbe6a077" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Method of Payment; Exchange Rate</font>. All amounts to be paid pursuant to this Agreement will be made in U.S. 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 Selling 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.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Blocked Payments</font>. If by reason of Applicable Law in any country or jurisdiction, it becomes impossible or illegal for a Party to transfer, or have transferred on its behalf, payments owed the other
              Party hereunder, then such Party will promptly notify the other Party of the conditions preventing such transfer and use reasonable efforts to deposit such payments in U.S. Dollars. If, after using reasonable efforts, such Party is not able
              to deposit such payments in U.S. Dollars, then 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 [***], 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>
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    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">33</font></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;" noshade="noshade"></div>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.10</td>
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            <div><font style="font-weight: bold;">Taxes</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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            <div><font style="font-weight: bold;">Taxes on Income</font>. Each Party will be solely responsible for the payment of any and all income Taxes levied on account of all payments it receives under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: 39.6pt; vertical-align: top;">9.10.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Withholding Tax</font>. Any and all payments made pursuant to this Agreement will be paid without deduction or withholding for any Taxes, except as required by Applicable Law. To the extent a Party is
              required by Applicable Law to deduct or withhold Taxes on any payment to the other Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Withheld Amount</font>&#8221;), such Party will remit such Withheld Amount to the proper
              Governmental Authority in a timely manner and promptly transmit to the other Party an official Tax certificate or other evidence of any withholding sufficient to enable the other Party to claim available credits for such Withheld Amount. The
              withholding Party will have the right to deduct such Withheld Amount from payment due to the other Party. For the avoidance of doubt, to the extent such Withheld Amount is so withheld and remitted in accordance with this <u>Section 9.10.2</u>
              (Withholding Tax), such Withheld Amount will be treated for all purposes of this Agreement as having been paid to the other Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Tax Cooperation</font>. The Parties agree to cooperate with one another in accordance with Applicable Law and use reasonable efforts to [***] in respect of payments made by each Party to the other Party
              under this Agreement. Without limiting the generality of the foregoing, each Party will provide the other with any Tax forms and other information that may be reasonably necessary to [***] based on an applicable treaty or otherwise, including
              a properly completed Internal Revenue Service (&#8220;<font style="font-weight: bold; font-style: italic;">IRS</font>&#8221;) Form W-9 or appropriate IRS Form W-8, as applicable, before a payment is made. If any Tax form or other information a Party
              previously delivered expires or becomes obsolete or inaccurate in any respect, then such Party will provide the other Party with an updated version of such form or certification or promptly notify the other Party in writing of its legal
              inability to do so. Each Party will provide the other Party with reasonable assistance to enable the recovery, as permitted by Applicable Law, of withholding Taxes or similar obligations resulting from payments made under this Agreement, such
              recovery to be for the benefit of the Party bearing such withholding Tax.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">9.10.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Changes in Domicile</font>. Notwithstanding any provision to the contrary in this Agreement, including <u>Section 9.10.2</u> (Withholding Tax), if as a result of a Party assigning, transferring, or
              conveying rights under this Agreement to an Affiliate or changing its domicile, additional Taxes become due that would not otherwise have been due hereunder with respect to payments under this Agreement, then such Party will be responsible
              for all such additional withholding Taxes.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.11</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Late Payments; Disputed Payments</font>. Any undisputed payments or portions thereof due hereunder that are not paid on or before the date such payments are due under this Agreement will bear interest from
              the due date until the date of payment at a per-annum rate equal to the lesser of: (a) [***] percentage points above the prime rate as published by <font style="font-style: italic;">The Wall Street Journal </font>or any successor thereto;
              or (b) the maximum rate permitted by Applicable Law. If a Party disputes an invoice or other payment obligation under this Agreement, then such Party will timely pay the undisputed amount of the invoice or other payment obligation, and the
              Parties will resolve such dispute in accordance with <u>Article 15</u> (Dispute Resolution; Governing Law).</div>
          </td>
        </tr>

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    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">34</font></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;" noshade="noshade"></div>
    </div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 10</div>
    <div style="text-align: center; font-weight: bold;">INTELLECTUAL PROPERTY</div>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Inventions</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ownership of 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
              Patent Rights and Know-How 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>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ownership of Arising Intellectual Property</font>. As between the Parties, ownership of all Collaboration Know-How will be as follows:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
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          <td style="width: 36pt; vertical-align: top;">(a)</td>
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            <div>Ionis will be the sole owner of any (i) Collaboration Know-How that is developed or invented solely by Representatives of Ionis or its Affiliates or its or their licensees (other than Otsuka), Sublicensees, or Subcontractors, or any
              Persons contractually required to assign or license such Collaboration Know-How to Ionis or any Affiliate of Ionis (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Know-How</font>&#8221;), and (ii) Patent Rights that Cover
              the Ionis Collaboration Know-How (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Patent Rights</font>&#8221;), and will retain all of its rights thereto, subject to any rights or licenses expressly granted by Ionis to
              Otsuka under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Otsuka will be the sole owner of any (i) Collaboration Know-How that is developed or invented solely by Representatives of Otsuka or its Affiliates or its or their licensees (other than Ionis), Sublicensees, or Subcontractors, or any
              Persons contractually required to assign or license such Collaboration Know-How to Otsuka or any Affiliate of Otsuka (&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Collaboration Know-How</font>&#8221;), and (ii) Patent Rights that
              Cover the Otsuka Collaboration Know-How (&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Collaboration Patent Rights</font>&#8221;), and will retain all of its rights thereto, subject to any rights or licenses expressly granted by
              Otsuka to Ionis under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Each Party will own an equal, undivided share of all Joint Collaboration Technology.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Disclosure; Inventorship</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 72pt;"><br>
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          <td style="width: 36pt; vertical-align: top;">(a)</td>
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            <div><font style="font-weight: bold;">Invention Disclosure</font>. Each Party will promptly disclose to the other Party all Inventions within the Collaboration Know-How developed or invented during the Term by or on behalf of such Party, in
              each case, as soon as practicable prior to an intended public disclosure of such Invention and prior to the filing of a patent application thereon. Each Party will also promptly respond to reasonable requests from the other Party for
              additional information relating thereto.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Inventions by a Party</font>. Inventorship for Inventions and discoveries (including Know-How) first invented or developed during the course of the performance of activities under this Agreement will be
              determined in accordance with United States Patent Laws for determining inventorship.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">35</font></div>
      <div class="BRPFPageBreak" style="page-break-after: always;">
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    </div>
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        <tr>
          <td style="width: 72pt;"><br>
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          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Joint Research Agreement under the Leahy-Smith America Invents Act</font>. If a Party intends to invoke its rights under 35 U.S.C. &#167; 102(c) of the Leahy-Smith America Invents Act, then it will notify the
              other Party and neither Party will make an election under such provision when exercising its rights under this <u>Article 10</u> (Intellectual Property) without the prior written consent of the other Party (such consent not to be
              unreasonably withheld, conditioned, or delayed), and 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;<font style="font-style: italic;">joint research agreement</font>&#8221; as defined in 35 U.S.C. &#167; 100(h).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.1.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Practice Under and Other Use of Joint Collaboration Technology</font>. Subject to the rights granted under and the restrictions set forth in this Agreement (including the licenses granted under <u>Article
                2</u> (Licenses)), each Party will be entitled to the free use and enjoyment of all Joint Collaboration Technology and neither Party will have any obligation to account to the other Party for profits, or to obtain any approval of the other
              Party to license, assign, or otherwise exploit any Joint Collaboration Technology by reason of joint ownership thereof. Each Party hereby waives any right it may have under the Applicable Law of any jurisdiction to require any such approval
              or accounting. To the extent any further consent is required to enable a Party to so license or exploit its interest in the Joint Collaboration Technology, the other Party will grant consent promptly upon request. Without limitation, each
              Party will cooperate with the other Party if the Parties determine to apply for U.S. or foreign patent protection for any Joint Collaboration Technology and will obtain the cooperation of the individual inventors of any such Joint
              Collaboration Technology<font style="font-weight: bold;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.1.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Representative Assignment</font>. Each Party and its Affiliates will, and will cause its licensees, Sublicensees and Subcontractors to, enter into an agreement or employment policy with each of its
              Representatives performing activities related to Development, Manufacture, or Commercialization of a Licensed Product that (a) compels prompt disclosure to such Party (or its Affiliate, licensee, Sublicensee or Subcontractor, as applicable)
              of all Collaboration Know-How and Collaboration Patent Rights discovered, developed, invented, or filed by such Representative during any performance of such Development, Manufacture or Commercialization activities; and (b) automatically
              assigns to such Party (or its Affiliate, licensee, Sublicensee or Subcontractor, as applicable) all rights, title, and interests in and to all Collaboration Know-How and Collaboration Patent Rights, and requires each Representative to execute
              all documents and take such other actions as may be necessary to effectuate such assignment (or, if such assignment is not feasible, provides for such Party&#8217;s (or its Affiliate&#8217;s, licensee&#8217;s, Sublicensee&#8217;s or Subcontractor&#8217;s, as applicable)
              joint ownership of, or an irrevocable, royalty-free license to such Party (or its Affiliate, licensee, Sublicensee or Subcontractor, as applicable) under, all Collaboration Know-How and Collaboration Patent Rights, with the right to
              sublicense to the other Party as contemplated in this Agreement), <font style="font-style: italic;">provided</font> that the foregoing will not apply with respect to improvements to background technology of a Subcontractor.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Patent Prosecution</font><font style="color: rgb(0, 0, 0);">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Patent Rights and Joint Collaboration Patent Rights</font>.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">36</font></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;" noshade="noshade"></div>
    </div>
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          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Right to Prosecute</font>. As between the Parties, Ionis will have the (i) first right, in its sole discretion, to control the Patent Prosecution of all Ionis Product-Specific Patents in the Otsuka
              Territory and all Joint Collaboration Patent Rights worldwide, and (ii) sole right, in its sole discretion, to control the Patent Prosecution of all (A) Ionis Product-Specific Patents in the Ionis Territory, and (B) Ionis Core Technology
              Patents and Ionis Manufacturing and Analytical Patents, in each case, worldwide (collectively, ((i) and (ii)), the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Prosecuted Patent Rights</font>&#8221;). Upon Ionis&#8217; request, Otsuka will
              obtain any necessary assignment documents for Ionis with respect to the Patent Prosecution of Ionis Prosecuted Patent Rights, will render all signatures that will be necessary for such patent filings, and will assist Ionis in all other
              reasonable ways that are necessary for the issuance of Ionis Prosecuted Patent Rights as well as for the Patent Prosecution of Ionis Prosecuted Patent Rights, and Ionis will reimburse Otsuka&#8217;s reasonable External Costs incurred in connection
              therewith. Ionis will be responsible for [***] of the costs and expenses incurred with respect to the Patent Prosecution of all Ionis Product-Specific Patents, Ionis Core Technology Patents and Ionis Manufacturing and Analytical Patents
              throughout the world and for [***] of the costs and expenses incurred with respect to the Patent Prosecution of Joint Collaboration Patent Rights in the Ionis Territory. Otsuka will be responsible for [***] of the reasonable out-of-pocket
              costs incurred by or on behalf of Ionis with respect to the Patent Prosecution of the Joint Collaboration Patent Rights in the Otsuka Territory (including any maintenance fees owed to local patent offices for the Joint Collaboration Patent
              Rights in the Otsuka Territory), and Otsuka will reimburse Ionis for such costs within [***] after receiving an invoice with reasonable supporting documentation for such costs.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd0dfcc92795342689a537413a1902c56" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Review and Consult</font>. Ionis will consult with Otsuka and keep Otsuka reasonably informed regarding the Patent Prosecution of the Ionis Product-Specific Patents in the Otsuka Territory and the Patent
              Prosecution of the Joint Collaboration Patent Rights worldwide and will provide Otsuka with all substantive correspondence received from any patent authority in connection therewith no later than [***] after receipt thereof. In addition,
              Ionis will provide Otsuka with drafts of proposed substantive filings in the Otsuka Territory and correspondence to any patent authority in the Otsuka Territory in connection with the Patent Prosecution of the Ionis Product-Specific Patents
              and with drafts of proposed substantive filings in the Territory and correspondence to any patent authority in the Territory in connection with the Patent Prosecution of Joint Collaboration Patent Rights, in each case for Otsuka&#8217;s review and
              comment at least [***] prior to the submission of such proposed filings and correspondence, which comments (if any) Otsuka must provide no later than [***] after receipt of the applicable filing or correspondence. Ionis will consider in good
              faith Otsuka&#8217;s reasonable comments on the Patent Prosecution of the Ionis Product-Specific Patents in the Otsuka Territory and the Joint Collaboration Patent Rights in the Territory, but Ionis will have final decision-making authority
              regarding Patent Prosecution of such Patent Rights under this <u>Section 10.2.1(b)</u> (Review and Consult).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z9764869f6dc5415d9c86ba145e766624" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Abandonment</font>. If, at any time during the Term, Ionis decides to cease the Patent Prosecution of a particular Ionis Product-Specific Patent in the Otsuka Territory, or a particular Joint Collaboration
              Patent Right in the Territory, then Ionis will provide written notice to Otsuka of such decision at least [***] prior to the date that such applicable Patent Right will become abandoned. Unless such written notice includes a reasonable
              strategic reason for ceasing such Patent Prosecution (e.g., continuing such Patent Prosecution would adversely affect Ionis&#8217; Patent Prosecution or litigation strategy), Otsuka may, upon written notice to Ionis, assume the Patent Prosecution
              of any such Patent Right at Otsuka&#8217;s sole cost and expense. Without limiting the foregoing, with respect to any such Joint Collaboration Patent Right abandoned by Ionis, Ionis shall assign, and hereby does assign, to Otsuka all of its rights,
              title and interests in and to such Joint Collaboration Patent Right, and upon such assignment, such Joint Collaboration Patent Right shall be deemed an Otsuka Patent Right for all purposes of this 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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">37</font></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;" noshade="noshade"></div>
    </div>
    <table id="z4832e698280942c6945073b6f9f9932d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka Patent Rights</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z2153b7488e934b7c969238d704557b3f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Right to Prosecute</font>. As between the Parties, Otsuka will have the first right to control the Patent Prosecution of all Otsuka Patent Rights throughout the world. Otsuka will be responsible for [***]
              of the costs and expenses incurred with respect to the Patent Prosecution of such Patent Rights throughout the world.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5796bb183399437ebd23a4cbf1f4ed7c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Review and Consult</font>. Otsuka will consult with Ionis and keep Ionis reasonably informed regarding the Patent Prosecution of the Otsuka Patent Rights and will provide Ionis with all substantive
              correspondence received from any patent authority in connection therewith no later than [***] after receipt thereof. In addition, Otsuka will provide Ionis with drafts of all proposed substantive filings and correspondence to any patent
              authority in connection with the Patent Prosecution of the Otsuka Patent Rights for Ionis&#8217; review and comment at least [***] prior to the submission of such proposed filings and correspondence, which comments (if any) Ionis must provide no
              later than [***] after receipt of the applicable filing or correspondence. Otsuka will consider in good faith Ionis&#8217; reasonable comments on the Patent Prosecution of the Otsuka Patent Rights, but will have final decision-making authority
              regarding Patent Prosecution of such Patent Rights under this <u>Section 10.2.1(b)</u> (Review and Consult).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zad4eb47c1d584656b0b93cecb0334003" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Abandonment</font>. If, at any time during the Term, Otsuka ceases the Patent Prosecution of a particular Otsuka Patent Right, then Otsuka will provide written notice to Ionis of such decision at least
              [***] prior to the date on which such Patent Right will become abandoned. Unless such written notice includes a reasonable strategic reason for ceasing such Patent Prosecution (e.g., continuing such Patent Prosecution would adversely affect
              Otsuka&#8217;s Patent Prosecution or litigation strategy), Ionis may, upon written notice to Otsuka, assume the Patent Prosecution of any such Patent Right at Ionis&#8217; sole cost and expense.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z98a2a2d13390433296dd514cd7729029" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Enforcement Against Third Party Infringement or Misappropriation</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc78bbe87747449728713d1bf39f7876d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.3.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Notice of Infringement or Misappropriation</font>. Each Party will promptly notify the other of any apparent, threatened, or actual Competitive Infringement of which it becomes aware.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">38</font></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;" noshade="noshade"></div>
    </div>
    <table id="zcc2be0a6cb75435ebbf27bb86e845f3f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka&#8217;s Enforcement Right</font>. Otsuka will have the first right, but not the obligation, to enforce [***] against any Competitive Infringement in the Otsuka Territory and at its own cost and expense and
              using counsel of its own choice; <font style="font-style: italic;">provided </font>that, (a) [***] Ionis will be entitled to attend any substantive meetings, hearings, or other proceedings related to such infringement or misappropriation
              suit (together with its own counsel, at its own expense) and to review and comment on all substantive documents related to such infringement or misappropriation suit prior to filing or submission of such documents, and (b) with respect [***]
              Otsuka shall keep Ionis reasonably informed of the status of any substantive meetings, hearings, or other proceedings related to such infringement or misappropriation suit. If Otsuka fails to initiate a suit or take other action to abate any
              such Competitive Infringement within the earlier of: (i) [***] and (ii) [***], then, in either case, Ionis will have the second right, but not the obligation, to attempt to resolve such Competitive Infringement, at its own expense, including
              the filing of an infringement or misappropriation suit, as applicable, to enforce the applicable Patent Rights or Know-How using counsel of its own choice; <font style="font-style: italic;">provided </font>that, if Otsuka notifies Ionis
              during [***] that it is electing not to take steps to enforce the applicable Patent Rights against such Competitive Infringement [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z733b5c41ee5a4289b1ea1ca9b6fd8351" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.3.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis&#8217; Enforcement Right</font>. Ionis will have the sole right, but not the obligation, to enforce [***] against any Competitive Infringement in the Territory, in each case ((a) and (b)), at its own cost
              and expense and using counsel of its own choice; <font style="font-style: italic;">provided </font>that Ionis shall keep Otsuka reasonably informed of the status of any substantive meetings, hearings, or other proceedings related to any
              infringement or misappropriation suit to enforce [***] against any Competitive Infringement in the Otsuka Territory. Ionis will have the first right, but not the obligation, to enforce any [***] in the Ionis Territory, in each case, at its
              own expense and using counsel of its own choice; <font style="font-style: italic;">provided </font>that Otsuka will be entitled to attend any substantive meetings, hearings, or other proceedings related to such infringement or
              misappropriation suit (together with its own counsel, at its own expense) and to review and comment on all substantive documents related to such infringement or misappropriation suit prior to filing or submission of such documents. If Ionis
              fails to initiate a suit or take other action to abate any such Competitive Infringement with respect to [***] in the Ionis Territory within the earlier of: (a) [***] and (b) [***], then, in either case, Otsuka will have the second right, but
              not the obligation, to attempt to resolve such Competitive Infringement, at its own expense, including the filing of an infringement or misappropriation suit, as applicable, to enforce the applicable Otsuka Technology or Joint Collaboration
              Technology using counsel of its own choice; <font style="font-style: italic;">provided </font>that, if Ionis notifies Otsuka during [***] that it is electing not to take steps to enforce the applicable Patent Rights against such Competitive
              Infringement [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z9b9477da52d347ad96c1cd2cfcbee207" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.3.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Allocation of Recoveries</font>. Any recoveries resulting from an enforcement action relating to a claim of Competitive Infringement in the Territory will be first applied against payment of each Party&#8217;s
              costs and expenses in connection therewith. Any such recoveries in excess of such costs and expenses will be [***]; <font style="font-style: italic;">provided</font> that [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="ze6692071a24349719fc09539b2d06d48" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.3.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cooperation; Procedures</font>. At the request and expense of the Party bringing an infringement or misappropriation action under this <u>Section 10.3</u> (Enforcement Against Third Party Infringement or
              Misappropriation), the other Party will provide reasonable assistance and cooperation in any such action (including entering into a common interest agreement if reasonably deemed necessary by any Party) and agrees to be joined as a party to
              the suit if necessary for the initiating Party to bring or continue an infringement or misappropriation action hereunder. In addition, the Party bringing an infringement or misappropriation action under this <u>Section 10.3</u> (Enforcement
              Against Third Party Infringement or Misappropriation) will provide the other Party with copies of all pleadings and other documents in advance of filing with the court and will consider reasonable input from the other Party during the course
              of the action. For clarity, the Party bringing an infringement or misappropriation action under this <u>Section 10.3</u> (Enforcement Against Third Party Infringement or Misappropriation) will control such infringement or misappropriation
              action subject to the terms of this <u>Section 10.3</u> (Enforcement Against Third Party Infringement or Misappropriation). Neither Party may settle any action or proceeding brought under this <u>Section 10.3</u> (Enforcement Against Third
              Party Infringement or Misappropriation) or knowingly take any other action in the course thereof that disclaims, limits the scope of, admits the invalidity or unenforceability of, or grants a license, covenant not to sue or similar immunity
              under a Patent Right Controlled by the other Party without first obtaining the written consent of the Party that Controls the relevant Patent Right. Furthermore, Ionis may not [***]. The Parties will reasonably assist each other and cooperate
              with each other, at their own expense, in any such investigation, pre-litigation preparation, or litigation to ensure that there is an aligned global litigation and enforcement strategy.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">39</font></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;" noshade="noshade"></div>
    </div>
    <table id="z9a093aa547554c10a872882d22316867" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Defense of Third-Party Patent Challenges</font>. Each Party will promptly notify the other Party in writing after becoming aware of an actual or threatened Patent Challenge by a Third Party of any Ionis
              Patent Right, Otsuka Patent Right, and Joint Collaboration Patent Right (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Third Party Patent Challenge</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc1f13d37f59c4f8bbebe53488f3dbdd7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.4.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka&#8217;s Right to Defend</font>. Subject to the terms of <u>Section 10.4.3</u> (Cooperation; Procedures), and except as may be otherwise agreed by the Parties, Otsuka will have the first right, but not the
              obligation, to control the defense of any Third Party Patent Challenge relating to an Otsuka Patent Right or Joint Collaboration Patent Right in the Otsuka Territory, and to compromise, litigate, settle, or otherwise dispose of any such
              challenge, in each case at its own expense using counsel of its own choice; <font style="font-style: italic;">provided </font>that (a) with respect to a Joint Collaboration Patent Right, Ionis will be entitled to attend any substantive
              meetings, hearings, or other proceedings related to such Third Party Patent Challenge (together with its own counsel, at its own expense) and to review and comment on all substantive documents related to such Third Party Patent Challenge, and
              (b) with respect to an Otsuka Patent Right, Otsuka shall keep<font style="font-style: italic;">&#160;</font>Ionis reasonably informed of the status of any substantive meetings, hearings, or other proceedings related to such Third Party Patent
              Challenge, and if Otsuka fails to initiate the defense of such Third Party Patent Challenge of a Patent Right in the Otsuka Territory within [***] after the notice provided under <u>Section 10.4</u> (Defense of Third Party Patent
              Challenges), or otherwise abandons or elects not to continue any such defense once initiated, then Ionis will have the second right, but not the obligation, to control the defense of such Third Party Patent Challenge at its own expense using
              counsel of its own choice.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z382f385b552b4b6f95f8678469f9f4c0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.4.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis&#8217; Right to Defend</font>. Ionis will have the sole right, but not the obligation, to control the defense of any Third Party Patent Challenge relating to an (a) Ionis Product-Specific Patent in the
              Ionis Territory or (b) Ionis Core Technology Patent or Ionis Manufacturing and Analytical Patent in the Territory, and to compromise, litigate, settle, or otherwise dispose of any such challenge, in each case, at its own expense using counsel
              of its own choice. Subject to the terms of <u>Section 10.4.3</u> (Cooperation; Procedures), Ionis will have the first right, but not the obligation, to control the defense of any Third Party Patent Challenge relating to an (i) Otsuka Patent
              Right or Joint Collaboration Patent Right in the Ionis Territory or (ii) Ionis Product-Specific Patent in the Otsuka Territory and to compromise, litigate, settle, or otherwise dispose of any such challenge, at its own expense using counsel
              of its own choice; <font style="font-style: italic;">provided </font>that Otsuka will be entitled to attend any substantive meetings, hearings, or other proceedings related to such Third Party Patent Challenge (together with its own
              counsel, at its own expense) and to review and comment on all substantive documents related to such Third Party Patent Challenge. If Ionis fails to initiate the defense of such Third Party Patent Challenge of an Otsuka Patent Right or Joint
              Collaboration Patent Right in the Ionis Territory or an Ionis Product-Specific Patent in the Otsuka Territory, in each case, within [***] after the notice provided under <u>Section 10.4</u> (Defense of Third Party Patent Challenges), or
              otherwise abandons or elects not to continue any such defense once initiated, then Otsuka will have the second right, but not the obligation, to control the defense of such Third Party Patent Challenge at its own expense using counsel of its
              own choice.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">40</font></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;" noshade="noshade"></div>
    </div>
    <table id="zafbb4467aaa44eacb4789b451d98eb59" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.4.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cooperation; Procedures</font>. At the request and expense of the Party controlling the defense of any Third Party Patent Challenge under this <u>Section 10.4</u> (Defense of Third Party Patent
              Challenges), the other Party will provide reasonable assistance and cooperation in any such action. In addition, the Party controlling the defense of any Third Party Patent Challenge under this <u>Section 10.4</u> (Defense of Third Party
              Patent Challenges) will provide the other Party with copies of all pleadings and other documents to be filed with the court and will consider reasonable input from the other Party during the course of the action. Otsuka may not settle any
              action or proceeding brought or defended under this <u>Section 10.4</u> (Defense of Third-Party Patent Challenges) or knowingly take any other action in the course thereof without Ionis&#8217; prior written consent, unless such action or
              proceeding solely concerns the Otsuka Patent Rights. Ionis may not settle any action or proceeding brought or defended under this <u>Section 10.4</u> (Defense of Third-Party Patent Challenges) or knowingly take any other action in the course
              thereof with respect to the Ionis Product-Specific Patents or Joint Collaboration Patent Rights in the Otsuka Territory, without Otsuka&#8217;s prior written consent not to be unreasonably withheld, conditioned or delayed. The Parties will
              reasonably assist each other and cooperate with each other, at their own expense, in any such investigation, pre-litigation preparation, or litigation to ensure that there is an aligned global litigation strategy. Notwithstanding the above,
              in the case of any invalidity or unenforceability claims arising in an enforcement action under <u>Section 10.3</u> (Enforcement Against Third Party Infringement or Misappropriation), the Party controlling the enforcement action pursuant to
              <u>Section 10.3</u> (Enforcement Against Third Party Infringement or Misappropriation) shall control the response to such invalidity or unenforceability claims, <font style="font-style: italic;">provided</font> such Party may not admit
              invalidity or unenforceability of any Patent Right Controlled by the other Party without the prior written consent of the other Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z24fb9d341f9b454090d802348d8e87d2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Third Party Infringement Claims</font><font style="color: rgb(0, 0, 0);">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.5.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Infringement Claim; Patent Challenges of Third-Party IP</font>. If a Third Party asserts that a Patent Right controlled by it is, or will be, infringed by the Exploitation of a Licensed Product in the
              Territory in accordance with this Agreement, then the Party first obtaining knowledge of such claim will promptly provide the other Party with prompt written notice thereof and the related facts in reasonable detail.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc6871c809280418a95b731ad9887b4b6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.5.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Responsibility to Defend</font>. During the Term of this Agreement, if a Third Party asserts that a Patent Right controlled by such Third Party is infringed, or will be infringed, by the Exploitation of a
              Licensed Product, then the Parties will promptly discuss the matter and the appropriate course of action. If the Parties cannot agree on a course of action within [***] following the date on which the Parties receive notice of such Third
              Party claim, then, subject to <u>Article 13</u> (Indemnification): (a) Ionis will have the sole right, but not the obligation, to defend such claim in the Ionis Territory using counsel of its own choosing, and (b) Otsuka will have the first
              right, but not the obligation, to defend such claim in the Otsuka Territory using counsel of its own choosing. If Otsuka does not take affirmative steps to defend such claim in the Otsuka Territory within [***] (or such shorter period of time
              as is legally required to answer to such claim) and does not inform Ionis within such [***] period that it is electing not to defend such claim for strategic reasons intended to maintain the commercial value of the relevant Patent Rights or
              any product or subject matter Covered thereby or relating thereto, then Ionis may defend such claim in the Otsuka Territory. The Party defending such claim in the Otsuka Territory will (i) keep the other Party reasonably informed regarding
              any such assertion, including by providing the other Party with copies of all pleadings and other documents filed in any proceeding relating to such claim, (ii) consider reasonable input from the other Party during the course of the claim,
              and (iii) provide the other Party with the opportunity to attend any substantive meetings, hearings, or other proceedings related to such claim (together with its own counsel, at its own expense) and to review and comment on all substantive
              documents related to such claim prior to filing or submission of such documents. The Parties will reasonably assist each other and cooperate and share information with respect to any such claim. Each Party will bear its own costs and expenses
              with respect to any such claim.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">41</font></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;" noshade="noshade"></div>
    </div>
    <table id="ze7824cdc72084e1ba6497e37ec56fe09" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.5.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Settlement</font>. Subject to <u>Article 13</u> (Indemnification), neither Party will pursue or enter into any settlement or license agreement with any Third Party with respect to the Patent Rights that
              are the subject of a claim brought by a Third Party that a Patent Right controlled by such Third Party is infringed by the Exploitation of a Licensed Product in the Otsuka Territory without the other Party&#8217;s prior written consent, not to be
              unreasonably withheld, conditioned, or delayed. Subject to <u>Article 13</u> (Indemnification), Otsuka will bear the costs of any amounts paid in settlement or to satisfy a judgment of a claim that the Exploitation of a Licensed Product
              infringes any Third Party Patent Right in the Otsuka Territory, except to the extent such costs [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Patent Challenges of Third-Party Patent Rights</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd5e69424d28a4a92a5e94ebbe4bfaf77" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.6.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Notice of Third-Party Patent Right</font>. If either Party becomes aware of a Third Party Patent Right that might form the basis for a claim that the Exploitation of a Licensed Product anywhere in the world
              infringes, or will infringe, such Patent Right, then the Party first obtaining knowledge of such Patent Right will promptly provide the other Party with written notice thereof and the related facts in reasonable detail, and the Parties will
              promptly meet to discuss the matter.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zfd1945ce01174f4e947a56d255862c95" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.6.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Patent Challenges of Third-Party Patents</font>. Ionis will have the sole right, but not the obligation, to initiate a Patent Challenge of any such Third Party Patent Right in the Ionis Territory using
              counsel of its own choosing. Otsuka will have the first right, but not the obligation, to initiate a Patent Challenge of such Third Party Patent Right in the Otsuka Territory, and if Otsuka notifies Ionis that it does not intend to initiate
              such a Patent Challenge, Ionis will have the second right, but not the obligation, to do so; <font style="font-style: italic;">provided </font>that, [***]. The Party initiating such Patent Challenge will (a) keep the other Party reasonably
              informed regarding any such Patent Challenge, including by providing the other Party with copies of all pleadings and other documents filed in any proceeding relating to such Patent Challenge, (b) consider reasonable input from the other
              Party during the course of the Patent Challenge, and (c) provide the other Party with the opportunity to attend any substantive meetings, hearings, or other proceedings related to such Patent Challenge (together with its own counsel, at its
              own expense) and to review and comment on all substantive documents related to such Patent Challenge prior to filing or submission of such documents. The Parties will reasonably assist each other and cooperate and share information with
              respect to any such Patent Challenge. Each Party will bear its own costs and expenses with respect to any such Patent Challenge; <font style="font-style: italic;">provided, however,</font> that the Parties will each bear [***] of the
              reasonable out-of-pocket costs incurred with respect to any such Patent Challenge in the Otsuka Territory, and the non-controlling Party will reimburse the Party initiating such Patent Challenge in the Otsuka Territory for such costs within
              [***] after receiving an invoice with reasonable supporting documentation for such costs.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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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;" noshade="noshade"></div>
    </div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.6.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Restrictions on Settlement</font>. Neither Party nor its Affiliates will pursue or enter into any settlement or license agreement with any Third Party with respect to the Patent Rights that are the subject
              of such Patent Challenge in the Otsuka Territory without the other Party&#8217;s prior written consent.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Patent Term Extensions</font>. With respect to any system for extending the term of Patent Rights in the Otsuka Territory established by any applicable Regulatory Authority during the Term that is similar
              to the patent term extension system in the U.S., [***] for making all decisions regarding patent term extensions of the Ionis Patent Rights or Joint Collaboration Patent Rights in the Otsuka Territory, including supplementary protection
              certificates and any other extensions that are now or become available in the future, that are applicable to the Ionis Patent Rights or Joint Collaboration Patent Rights licensed hereunder and that become available directly as a result of the
              Regulatory Approval of a Licensed Product in the Otsuka Territory; <font style="font-style: italic;">provided</font> that Otsuka will consult with Ionis with respect to such decisions and consider in good faith the reasonable comments and
              concerns of Ionis.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Unified Patent Court</font>. Otsuka will be solely responsible for making all decisions regarding the opting-out or opting-in of existing Patent Rights into the jurisdiction of the Unified Patent Court or
              the registration of Patent Rights with Unitary Effect; <font style="font-style: italic;">provided </font>that Otsuka will consult with Ionis with respect to such decisions and will consider the comments and concerns of Ionis in good faith.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Common Interest</font>. The Parties stipulate and agree that, with regard to such prosecution, maintenance, enforcement, and defense 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 stipulate and agree 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 any provision to the contrary set forth in this
              Agreement, 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>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Product Trademarks</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
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            <div><font style="font-weight: bold;">Ownershi</font>p.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Unitary Product Trademark</font>. Ionis shall, at its sole cost and expense, develop, and shall use Commercially Reasonable Efforts to obtain and maintain, a unitary Trademark (and back-up Trademarks
              thereof) to be used for the Licensed Products worldwide (the &#8220;<font style="font-weight: bold; font-style: italic;">Unitary Product Trademark</font>&#8221;); <font style="font-style: italic;">provided however</font>, [***]. Ionis will own all
              right, title, and interest in and to the Unitary Product Trademark. Otsuka will use the Unitary Product Trademark in the Otsuka Territory to the extent required by and in accordance with the Otsuka Territory Brand Strategic and Operating
              Plan, subject to <u>Section 6.4</u> (Global Brand Strategic and Operating Plan) and <u>Section 6.5</u> (Otsuka Territory Brand Strategic and Operating Plan).</div>
          </td>
        </tr>

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    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">43</font></div>
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        <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
    </div>
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            <div><font style="font-weight: bold;">Ownership of Otsuka Product Trademarks</font>. As between the Parties, Otsuka will have the sole right to determine and will own all right, title, and interest in and to any Trademarks, other than the
              Unitary Product Trademark, to be created or used by Otsuka or its Affiliates or its or their Sublicensees for the Exploitation of Licensed Product in the Otsuka Territory excluding any trademarks, service marks, names, or logos that include
              any corporate name or logo of the Parties or their Affiliates or its or their Sublicensees (&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Product Trademarks</font>&#8221;); <font style="font-style: italic;">provided </font>that
              such Otsuka Product Trademarks are consistent with the Global Brand Strategic and Operating Plan. Ionis will not [***]. Ionis will not [***].</div>
          </td>
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    </table>
    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Ownership of Ionis Product Trademarks</font>. As between the Parties, Ionis will have the sole right to determine and will own all right, title, and interest in and to the Trademarks (other than the Unitary
              Product Trademark) to be used by Ionis or its Affiliates or its or their Sublicensees or licensees for the Exploitation of Licensed Product in the Ionis Territory excluding any trademarks, service marks, names, or logos that include any
              corporate name or logo of the Parties or their Affiliates or its or their Sublicensees or licensees (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product Trademarks</font>&#8221;); <font style="font-style: italic;">provided</font>
              that such Ionis Product Trademarks are consistent with the Global Brand Strategic and Operating Plan.<font style="font-weight: bold; font-style: italic;">&#160;</font>Otsuka will not [***]. Otsuka will not [***].</div>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.10.2</td>
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            <div><font style="font-weight: bold;">Notice</font>. Each Party will provide to the other Party prompt written notice of any actual or threatened infringement of the Otsuka Product Trademarks or Ionis Product Trademarks in the Territory and of
              any actual or threatened claim that the use of the Otsuka Product Trademarks or Ionis Product Trademarks in the Territory violates the rights of any Third Party, in each case, of which such Party becomes aware.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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            <div><font style="font-weight: bold;">Prosecution of Product Trademarks</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Unitary Product Trademark</font>.<font style="font-weight: bold;">&#160;</font>Ionis shall be responsible, at its sole discretion and cost and expense using counsel of its own choice, for the filing,
              prosecution, registration and maintenance (including the defense of opposition proceedings and any equivalent proceedings and including any legal actions to prevent or exclude Third Party Trademark registrations that are confusingly similar
              to the Unitary Product Trademark) of the Unitary Product Trademark in the Territory throughout the Term. Ionis shall keep Otsuka informed of material progress with regard to the prosecution, registration, and maintenance of the Unitary
              Product Trademark in the Otsuka Territory, including the content and timing of the filing of the Unitary Product Trademark in the Otsuka Territory, [***], and Ionis shall [***] the Unitary Product Trademark in the Otsuka Territory<font style="font-weight: bold; font-style: italic;">.</font></div>
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    </table>
    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Otsuka Product Trademarks</font>. Otsuka will have the sole right to register, prosecute and maintain the Otsuka Product Trademarks in the Territory using counsel of its own choice. All costs and expenses
              of registering, prosecuting and maintaining the Otsuka Product Trademarks in the Territory will be borne solely by Otsuka.</div>
          </td>
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    </table>
    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">44</font></div>
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    </div>
    <div><br>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Product Trademarks</font>. Ionis will have the sole right to register, prosecute and maintain the Ionis Product Trademarks in the Territory using counsel of its own choice. All costs and expenses of
              registering, prosecuting and maintaining the Ionis Product Trademarks in the Territory will be borne solely by Ionis.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
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          <td style="width: 39.6pt; vertical-align: top;">10.10.4</td>
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            <div><font style="font-weight: bold;">Enforcement of Product Trademarks</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Unitary Product Trademark</font>.<font style="font-weight: bold;">&#160;</font>During the Term, each Party will promptly notify the other Party in writing of any alleged, threatened or actual infringement,
              dilution, misappropriation or other violation of or unfair trade practices or any other like offense by a Third Party relating to the Unitary Product Trademark in the Otsuka Territory (&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka

                Territory Trademark Infringement</font>&#8221;). Otsuka will have the first right, but not the obligation, to take any reasonable measures it deems appropriate with respect to any Otsuka Territory Trademark Infringement, using counsel of its own
              choice, and at its own cost and expense, including initiating or prosecuting an infringement, misappropriation or other appropriate suit or action to enforce the Unitary Product Trademark in the Otsuka Territory and, if requested by Otsuka,
              Ionis shall (i) join as a party to such suit or action and execute and cause its Affiliates to execute all documents necessary for Otsuka to initiate and maintain such suit or action and (ii) provide reasonable assistance to Otsuka in
              connection with such suit or action. Notwithstanding the foregoing, if Otsuka does not inform Ionis that it intends to initiate a suit or take other action against an Otsuka Territory Trademark Infringement within [***] after Otsuka becoming
              aware of such Otsuka Territory Trademark Infringement and does not [***] within such [***], then Ionis will have the second right, but not the obligation, to initiate a suit or take other action against such Otsuka Territory Trademark
              Infringement at its own cost and expense. Any recoveries resulting from such suit or other action will be first applied against payment of each Party&#8217;s costs and expenses in connection therewith. Any such recoveries in excess of such costs
              and expenses will be [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z3610fe89b71845a18ad486c95ab0fb9f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka Product Trademarks</font>. Otsuka will have the sole right to take such action as Otsuka deems necessary against a Third Party based on any alleged, threatened or actual infringement, dilution,
              misappropriation or other violation of or unfair trade practices or any other like offense relating to, the Otsuka Product Trademarks by a Third Party in the Territory, at its sole cost and expense and using counsel of its own choice. Otsuka
              will retain any damages or other amounts collected in connection therewith.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7b1dc62bb9884b4a82c356b9c58243d2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Product Trademarks</font>. Ionis will have the sole right to take such action as Ionis deems necessary against a Third Party based on any alleged, threatened or actual infringement, dilution,
              misappropriation or other violation of or unfair trade practices or any other like offense relating to, the Ionis Product Trademarks by a Third Party in the Territory, at its sole cost and expense and using counsel of its own choice. Ionis
              will retain any damages or other amounts collected in connection therewith.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z1df4a92678ca45c8a119d0d43831d64c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.10.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Third Party Claims</font>.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">45</font></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;" noshade="noshade"></div>
    </div>
    <table id="zebacbce3a3f84f6d904dd74b9c78c461" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Unitary Product Trademark</font>. If a Third Party brings suit alleging that Otsuka&#8217;s or its Affiliate&#8217;s or Sublicensee&#8217;s Exploitation of a Licensed Product in the Otsuka Territory infringes or will
              infringe such Third Party&#8217;s Trademarks or that the use or registration of the Unitary Product Trademark in the Otsuka Territory infringes, dilutes, misappropriates or otherwise violates any Trademark or other right of such Third Party (&#8220;<font style="font-weight: bold; font-style: italic;">Trademark Infringement Suit</font>&#8221;), then the Party against whom such suit is brought will promptly notify the other Party of such Trademark Infringement Suit and Otsuka will have the first
              right, but not the obligation, to defend such Trademark Infringement Suit using counsel of its own choice. If Otsuka does not take affirmative steps to defend such Trademark Infringement Suit within [***] (or such shorter period of time as is
              legally required to answer to such suit) and does not [***], then Ionis may defend such Trademark Infringement Suit. The Party defending such Trademark Infringement Suit will (i) keep the other Party reasonably informed regarding such suit,
              including by providing the other Party with copies of all pleadings and other documents filed in any proceeding relating to such suit, (ii) consider reasonable input from the other Party during the course of the suit, and (iii) provide the
              other Party with the opportunity to attend any substantive meetings, hearings, or other proceedings related to such suit (together with its own counsel, at its own expense) and to review and comment on all substantive documents related to
              such suit prior to filing or submission of such documents. The Parties will reasonably assist each other and cooperate and share information with respect to any such suit. The Parties will [***] all of the costs incurred by either Party in
              defending a Trademark Infringement Suit and any and all damages paid in settlement or to satisfy a judgment in a Trademark Infringement Suit. Neither Party will enter into any settlement of a Trademark Infringement Suit that is instituted or
              threatened to be instituted against the other Party without the other Party&#8217;s prior written consent, not to be unreasonably withheld, conditioned or delayed; <font style="font-style: italic;">provided</font> that such consent will not be
              required if such settlement includes a release of all liability in favor of, and does not impose any obligation on, the other Party and contains no admission of liability by such settling Party. Further, neither Party shall settle or
              compromise any Trademark Infringement Suit, or knowingly take any other action in the course thereof, in a manner that materially adversely affects the other Party&#8217;s rights or interests, without the other Party&#8217;s prior written consent.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z90dec7755306481b8d49eee47fec063e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka Product Trademarks</font>. Otsuka will have the sole right to defend against and settle any alleged, threatened or actual claim by a Third Party that the use or registration of the Otsuka Product
              Trademarks in the Territory infringes, dilutes, misappropriates or otherwise violates any Trademark or other right of that Third Party or constitutes unfair trade practices or any other like offense or any other claims as may be brought by a
              Third Party against a Party in connection with the use of the Otsuka Product Trademarks with respect to the Licensed Products in the Otsuka Territory, at its sole cost and expense and using counsel of its own choice. Otsuka will retain any
              damages or other amounts collected in connection therewith.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z6e3ea9e446024e109379b58bc97d8d81" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Product Trademarks</font>. Ionis will have the sole right to defend against and settle any alleged, threatened or actual claim by a Third Party that the use or registration of the Ionis Product
              Trademarks in the Territory infringes, dilutes, misappropriates or otherwise violates any Trademark or other right of that Third Party or constitutes unfair trade practices or any other like offense or any other claims as may be brought by a
              Third Party against a Party in connection with the use of the Ionis Product Trademarks with respect to the Licensed Products in the Ionis Territory, at its sole cost and expense and using counsel of its own choice. Ionis will retain any
              damages or other amounts collected in connection therewith.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">46</font></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;" noshade="noshade"></div>
    </div>
    <table id="z0231033325f745ebbd5856ea2dd12857" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.10.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Housemarks</font>. The Parties, through the JSC, in consultation with regulatory experts, will [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc7fa2b529d654e2aa5dc9843ae52bb01" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">10.10.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cooperation</font>. Each Party will, and will cause its Affiliates to, promptly assist and cooperate with the other Party, as may be reasonably requested by a Party from time to time, in connection with its
              activities set forth in this <u>Section 10.10</u> (Product Trademarks), including where necessary, furnishing a power of attorney solely for such purpose or joining in, or being named as a necessary party to, such action, and providing
              access to relevant documents and other evidence; <font style="font-style: italic;">provided</font> that, except as provided otherwise in this <u>Section 10.10</u> (Product Trademarks) with respect to [***], the requesting Party will
              reimburse the other Party for its [***] incurred in connection therewith.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 11</div>
    <div style="text-align: center; font-weight: bold;">REPRESENTATIONS, WARRANTIES, AND COVENANTS</div>
    <div>&#160;</div>
    <table id="zd5c45fc90ba6495da64d97b8b0dc4eb8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Mutual Representations and Warranties</font>. Each of Otsuka and Ionis hereby represents and warrants to the other Party as of the Effective Date that:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zbf64e7e7948040c8af9380ed34f1a00a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>It is a corporation or limited company duly organized, validly existing, and in good standing under the laws of the jurisdiction of its organization, and it has the full right, power, and authority to enter into this Agreement and to
              perform its obligations hereunder.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zfdced55b4f2d42689e7ad808265848aa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>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 have been obtained.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z3155b051cb2c4513a9139390acaf090a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The execution, delivery, and performance of this Agreement by it has been duly authorized by all requisite corporate action.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.1.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The execution and delivery of this Agreement and the performance of its obligations hereunder (a) do not conflict with or violate any requirement of Applicable Law or any provision of its articles of incorporation, bylaws, limited
              partnership agreement, or any similar instrument, as applicable, in any material way, and (b) do not conflict with, violate, or breach or constitute a default or require any consent under, any Applicable Law or any contractual obligation or
              court or administrative order by which it is bound.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.1.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="color: rgb(0, 0, 0);">It has not been </font>debarred or suspended under 21 U.S.C. &#167;335(a) or (b)<font style="color: rgb(0, 0, 0);">, is not the subject of a conviction described in Section 306 of the FD&amp;C Act,</font> has
              not been and is not excluded from a federal or governmental health care program, debarred from federal contracting, convicted of or pled <font style="font-style: italic;">nolo contendere</font> to any felony, or to any federal or state legal
              violation (including misdemeanors) relating to prescription drug products or fraud, is not subject to OFAC sanctions or on the OFAC list of specially designated nationals, <font style="color: rgb(0, 0, 0);">and is not subject to any similar
                sanction of any Governmental Authority in the Territory</font> (&#8220;<font style="font-weight: bold; font-style: italic;">Debarred/Excluded</font>&#8221;)<font style="color: rgb(0, 0, 0);">, and no proceeding that could result in it being
                Debarred/Excluded is pending, and neither it nor any of its Affiliates has used, in any capacity in the performance of obligations relating to the Licensed Products, any </font>employee, <font style="color: rgb(0, 0, 0);">subcontractor,
                consultant, </font>agent, representative, <font style="color: rgb(0, 0, 0);">or other Person who has been Debarred/Excluded</font>.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">47</font></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;" noshade="noshade"></div>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Additional Ionis Representations and Warranties</font>. Ionis hereby represents and warrants as of the Effective Date to Otsuka that:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>It has the right under the Ionis Technology to grant to Otsuka the licenses set forth in this Agreement, and it has not granted any license or other right under the Ionis Technology that is inconsistent with the licenses granted to Otsuka
              hereunder.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-variant: small-caps; color: rgb(0, 0, 0);"><u>Schedule 1.91</u></font><font style="color: rgb(0, 0, 0);"> (Ionis Core Technology Patents), </font><font style="font-variant: small-caps;"><u>Schedule 1.96</u></font> (Ionis
              Manufacturing and Analytical Patents), and <font style="font-variant: small-caps;"><u>Schedule 1.103</u></font> (Ionis Product-Specific Patents), collectively, list all Ionis Patent Rights existing as of the Effective Date. With respect to
              any such Ionis Patent Right identified as being solely owned by Ionis, Ionis owns all rights, title, and interests in and to such Ionis Patent Rights.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>As of the Effective Date, all issued Patent Rights within the Ionis Patent Rights are in full force and effect and, to Ionis&#8217; Knowledge, are valid and enforceable. To Ionis&#8217; Knowledge, all Ionis Patent Rights&#160;are being diligently
              prosecuted in the respective patent offices in the Otsuka Territory in accordance with Applicable Law and have been filed, prosecuted and maintained properly and correctly, and all applicable fees have been paid on or before the due date for
              payment.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5a8b656e771f4162a19f17a4ca51aa64" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>There is no pending or, to Ionis&#8217; Knowledge, threatened litigation, nor has Ionis received any written notice from any Third Party, asserting or alleging that the Exploitation of the Licensed Products prior to the Effective Date infringed
              or misappropriated the Patent Rights, Know-How or other intellectual property rights of such Third Party or that the disclosing, copying, making, assigning, licensing or use of the Ionis Technology infringes or misappropriates any Patent
              Right, Know-How or other intellectual property rights of such Third Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>To Ionis&#8217; Knowledge, the practice by Otsuka of the Ionis Technology and the Exploitation by Otsuka or its Affiliates or Sublicensee of the Licensed Products in the form existing as of the Effective Date for the treatment of HAE, in each
              case, does not and will not infringe, misappropriate or otherwise violate any Patent Rights, Know-How or other intellectual property rights of any Third Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z1d7a073b6327495dabfb98940285cfa7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>To Ionis&#8217; Knowledge, there are no Third Party Know-How or Patent Rights that are necessary for the Exploitation of Licensed Products in the form existing as of the Effective Date for the treatment of HAE in the Otsuka Territory, other than
              the Know-How and Patent Rights licensed to Ionis pursuant to the Existing Third-Party IP Agreements. To Ionis&#8217; Knowledge, other than the Patent Rights and Know-How licensed to Ionis pursuant to the Existing Third-Party IP Agreements, there
              are no Third Party Patent Rights that Cover the composition of matter of Licensed Compound or Licensed Products or any Third Party Patent Rights or Know-How that are used in the Manufacture of the Licensed Product in the form existing as of
              the Effective Date.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
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            <div>There are no pending or, to Ionis&#8217; Knowledge, threatened, adverse actions, suits, or proceedings against Ionis involving the Ionis Technology.</div>
          </td>
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    <div>&#160;</div>
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        <tr>
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            <div>To Ionis&#8217; Knowledge, no Person is infringing or threatening to infringe or misappropriating or threatening to misappropriate any Ionis Technology in the Otsuka Territory.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>There are no legal claims, judgments, or settlements against or owed by Ionis or any of its Affiliates, or pending or, to Ionis&#8217; Knowledge, threatened, legal claims or litigation, in each case, relating to antitrust, anti-competition, or
              anti-corruption law violations.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: 39.6pt; vertical-align: top;">11.2.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-variant: small-caps;"><u>Schedule</u></font><u> 1.49</u> (Existing Third-Party IP Agreements) sets forth all Existing Third-Party IP Agreements in effect as of the Effective Date, redacted copies of which have been
              provided to Otsuka prior to the date hereof. Other than the Existing Third-Party IP Agreements set forth in <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 1.49</u> (Existing Third-Party IP Agreements), as of the Effective
              Date there are no agreements between Ionis and any Third Party pursuant to which Ionis Controls any Know-How or Patent Rights within the Ionis Technology.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Except for Existing Third-Party IP Agreements, Ionis is not obligated under any contract or other agreement with a Third Party as of the Effective Date to make any payments to any owner or licensor of, or other claimant to, any Patent
              Right, Know-How or other intellectual property or proprietary right with respect to the Exploitation of the Licensed Product in the Otsuka Territory in the form existing as of the Effective Date for the treatment of HAE.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.12</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>With respect to the Existing Third-Party IP Agreements, Ionis represents and warrants to Otsuka, as of the Effective Date, that: (a) it is in full force and effect; (b) neither Ionis nor any of its Affiliates is in material breach thereof;
              (c) neither Ionis nor any of its Affiliates has received any notice from any counterparties thereto of any material breach or notice of threatened material breach thereof; (d) neither Ionis nor any of its Affiliates has received any notice
              from any counterparties thereto of any intent to reduce the scope of the field thereunder or render any of the licenses thereunder non-exclusive or otherwise terminate such Existing Third-Party IP Agreements, and, to Ionis&#8217;s Knowledge no
              event, act or omission has occurred which would reasonably give rise to the right of any counterparties thereto to reduce the scope of the field thereof or render any of the licenses thereunder non-exclusive or otherwise terminate such
              agreement or any licenses thereunder (including with respect to any particular Patent Rights or other intellectual property); (e) neither Ionis nor any of its Affiliates have waived or relinquished any rights thereunder; (f) entering into
              this Agreement and granting the rights and licenses granted (or purported to be granted) to Otsuka hereunder complies with and will not result in a breach of the terms and conditions of any Existing Third-Party IP Agreement; and (g) Ionis has
              the right to grant sublicenses to Otsuka under the Existing Third-Party IP Agreements as contemplated herein, including to Develop, Manufacture, Commercialize and conduct Medical Affairs for the Licensed Products in the Field in the Otsuka
              Territory.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.13</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Neither Ionis nor any counterparty to any Existing Third-Party IP Agreement has in writing alleged or threatened that the other party has breached an Existing Third-Party IP Agreement (which has not been cured) or, to Ionis&#8217; Knowledge,
              threatened in writing to terminate an Existing Third-Party IP Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zfc66d194a53049168e9ce8b90b6bdb11" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.14</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Each [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.15</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>to Ionis&#8217; Knowledge: (a) [***]; and (b) [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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    </div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.16</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>All preclinical and clinical studies of the Licensed Products sponsored by Ionis or its Affiliates have been and as of the Effective Date are being conducted in material compliance with Applicable Law, including [***]. Neither Ionis nor
              its Affiliates has received any written notice from the FDA, the EMA, or any other Regulatory Authority performing functions similar to those performed by those with respect to any ongoing clinical or pre-clinical studies or tests of the
              Licensed Products requiring the termination, suspension, or material modification of such ongoing studies or tests, and no Governmental Authority has commenced any action to place a clinical hold order on, or otherwise terminate or suspend,
              any ongoing Clinical Trial of the Licensed Products conducted by or on behalf of Ionis or its Affiliates as of the Effective Date.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.2.17</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>As of the Effective Date, neither Ionis nor any of its Affiliates, and, to Ionis&#8217; Knowledge, none of its or their respective officers, employees, or agents, has made an untrue statement of material fact or fraudulent statement to the FDA
              or any other Regulatory Authority with respect to the Development of the Licensed Compounds or the Licensed Products, failed to disclose a material fact required to be disclosed to the FDA or any other Regulatory Authority with respect to the
              Development of the Licensed Compounds or the Licensed Products, or committed an act, made a statement, or failed to make a statement with respect to the Development of the Licensed Compounds or the Licensed Products that could reasonably be
              expected to provide a basis for the FDA to invoke its policy respecting &#8220;Fraud, Untrue Statements of Material Facts, Bribery, and Illegal Gratuities&#8221;, set forth in 56 Fed. Reg. 46191 (September 10, 1991) and any amendments thereto or any
              analogous laws or policies in the Otsuka Territory.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>As of the Effective Date, Ionis has no Knowledge of [***] in the Territory in the form existing as of the Effective Date for the treatment of HAE.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Additional Otsuka Representations and Warranties</font>. Otsuka represents and warrants to Ionis as of the Effective Date that there are no Patent Rights Controlled by Otsuka or any of its Affiliates that
              are necessary to Exploit a Licensed Product.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Additional Covenants</font>. Each of Otsuka and Ionis hereby covenant to the other:</div>
          </td>
        </tr>

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    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Assignment of Inventions</font>. Each Party will require all of its and its Affiliates&#8217; employees and consultants to assign all Inventions that are developed or invented by such employees according to the
              ownership principles described in <u>Section 10.1</u> (Inventions).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">11.4.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Compliance with Law</font>. It will, and will ensure that its Affiliates, comply with all Applicable Law and, to the extent applicable, Professional Requirements, with respect to the performance of its
              obligations under this Agreement, including, as applicable, the Approved Labeling,<font style="color: rgb(0, 0, 0);"> the European Data Protection Directive 95/46/EC, the European General Data Protection Regulation (Regulation (EU) 2016/679),
                and any other applicable national data protection legislation.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Bribery</font>. It will not in the future offer, promise, pay, authorize, or give, money or anything of value, directly or indirectly, to any Government Official or Other Covered Party for the purpose,
              pertaining to this Agreement, of: (a) influencing any act or decision of the Government Official or Other Covered Party; (b) inducing the Government Official or Other Covered Party to do or omit to do an act in violation of a lawful duty; (c)
              securing any improper advantage; or (d) inducing the Government Official or Other Covered Party to influence the act or decision of a government or government instrumentality, in order to obtain or retain business, or direct business to, any
              Person, in each case, in any way related to this Agreement.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">50</font></div>
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        <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
    </div>
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          <td style="width: 36pt;"><br>
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            <div><font style="font-weight: bold;">Restricted Countries</font>. Neither it nor its Affiliates will export, transfer, or sell any Licensed Product (a) to any country or territory that is subject to comprehensive economic sanctions
              administered by OFAC, unless the sale of such Licensed Product would be permissible if Otsuka or its Affiliates or Sublicensees were subject to OFAC&#8217;s jurisdiction, (b) to any other country or territory in which such activity would violate
              Applicable Law in the U.S., (c) to any Restricted Party unless the sale of such Licensed Product would be permissible if Otsuka or its Affiliates or Sublicensees was subject to OFAC&#8217;s jurisdiction, or (d) in such a manner that would violate
              the Global Trade Control Laws.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">FCPA Compliance</font>. In performing under this Agreement, it and its Affiliates agree to comply with all applicable anti-corruption laws, including the Foreign Corrupt Practices Act of 1977<font style="color: rgb(0, 0, 0);"> and the UK Bribery Act 2010</font>, as amended from time-to-time; the anti-corruption laws of the Territory; and all laws enacted to implement the Organization for Economic Co-operation and Development
              Convention on Combating Bribery of Foreign Officials in International Business Transactions.</div>
          </td>
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    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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            <div><font style="font-weight: bold;">Debarred/Excluded Persons</font>. It will not engage, in any capacity in connection with this Agreement or any ancillary agreements, any officer, employee, contractor, consultant, agent, representative, or
              other Person who has been Debarred/Excluded. Each Party will inform the other Party in writing promptly if it or any Person engaged by it or any of its Affiliates who is performing any obligations under this Agreement or any ancillary
              agreements is Debarred/Excluded, or if any action, suit, claim, investigation, or legal or administrative proceeding is pending or, to each Party&#8217;s Knowledge, is threatened, pursuant to which a Party, any of its Affiliates or any such Person
              performing obligations hereunder or thereunder may become Debarred/Excluded.</div>
          </td>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.5</td>
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            <div><font style="font-weight: bold;">Disclaimer</font>. EXCEPT AS EXPRESSLY SET FORTH HEREIN, THE INTELLECTUAL PROPERTY RIGHTS PROVIDED BY EACH PARTY ARE PROVIDED &#8220;AS IS&#8221; AND WITHOUT WARRANTY. EXCEPT AS EXPRESSLY SET FORTH HEREIN, EACH OF THE
              PARTIES EXPRESSLY DISCLAIMS ANY AND ALL WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING THE WARRANTIES OF DESIGN, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, VALIDITY, OR ENFORCEABILITY OF THEIR RESPECTIVE INTELLECTUAL PROPERTY
              RIGHTS, AND NONINFRINGEMENT OF THE INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES, ARISING FROM A COURSE OF DEALING, USAGE, OR TRADE PRACTICES, IN ALL CASES WITH RESPECT THERETO.</div>
          </td>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.6</td>
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            <div><font style="font-weight: bold;">Limitation of Liability</font>. NEITHER OF THE PARTIES WILL BE ENTITLED TO RECOVER FROM THE OTHER PARTY ANY SPECIAL, INCIDENTAL, INDIRECT, CONSEQUENTIAL, OR PUNITIVE DAMAGES OR DAMAGES FOR LOSS OF PROFIT,
              LOSS OF REVENUE, OR LOST OPPORTUNITY IN CONNECTION WITH THIS AGREEMENT, ITS PERFORMANCE OR LACK OF PERFORMANCE HEREUNDER, OR ANY LICENSE GRANTED HEREUNDER, EXCEPT TO THE EXTENT THE DAMAGES RESULT FROM A BREACH OF THE OBLIGATIONS OF A PARTY
              UNDER <u>ARTICLE 12</u> (CONFIDENTIALITY) OR BREACH OF <u>SECTION 2.5.2</u> (NEGATIVE COVENANT) BY IONIS, MISAPPROPRIATION OR INFRINGEMENT OF INTELLECTUAL PROPERTY OWNED OR CONTROLLED BY THE OTHER PARTY, OR AMOUNTS REQUIRED TO BE PAID TO A
              THIRD PARTY AS PART OF A CLAIM FOR WHICH A PARTY PROVIDES INDEMNIFICATION UNDER <u>ARTICLE 13</u> (INDEMNIFICATION).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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    <div style="text-align: center; font-weight: bold;">ARTICLE 12</div>
    <div style="text-align: center; font-weight: bold;">CONFIDENTIALITY</div>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.1</td>
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            <div><font style="font-weight: bold;">Duty of Confidence</font>. Subject to the other provisions of this <u>Article 12</u> (Confidentiality):</div>
          </td>
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    </table>
    <div>&#160;</div>
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        <tr>
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          <td style="width: 39.6pt; vertical-align: top;">12.1.1</td>
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            <div>except to the extent expressly authorized by this Agreement, the Receiving Party shall maintain in confidence and otherwise safeguard, and not publish or otherwise disclosed, all Confidential Information of the Disclosing Party;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
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            <div>the Receiving Party will treat all Confidential Information provided by the Disclosing Party, at a minimum, with the same degree of care as the Receiving Party uses for its own similar information, but in no event less than a reasonable
              degree of care;</div>
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    <div>&#160;</div>
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        <tr>
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            <div>the Receiving Party may only use any Confidential Information of the Disclosing Party for the purposes of performing its obligations or exercising its rights under this Agreement;</div>
          </td>
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    <div>&#160;</div>
    <table id="z1f011d3fb8b2440f93df40cd45c52fe1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
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            <div>a Receiving Party may only disclose Confidential Information of the Disclosing Party to: (a) such Receiving Party&#8217;s Affiliates, licensees, and Sublicensees; and (b) employees, directors, officers, agents, contractors, attorneys,
              accountants and consultants, of the Receiving Party and its Affiliates, licensees, and Sublicensees, in each case ((a) and (b)), to the extent reasonably necessary for the purposes of, and for those matters undertaken pursuant to, this
              Agreement; <font style="font-style: italic;">provided </font>that such Persons are bound by legally enforceable obligations of confidentiality and non-use with respect to the Disclosing Party&#8217;s Confidential Information, no less stringent
              than the confidentiality and non-use obligations set forth in this Agreement, except that the term of such obligation will be customary for such recipient of Confidential Information. Each Party will remain responsible for any failure by its
              Affiliates, licensees, and Sublicensees, and its and its Affiliates&#8217;, licensees&#8217;, and Sublicensees&#8217; respective employees, directors, officers, agents, consultants, attorneys, accountants and contractors, in each case, to treat such
              Confidential Information as required under this <u>Section 12.1</u> (Duty of Confidence) (as if such Persons were Parties directly bound to the requirements of this <u>Section 12.1</u> (Duty of Confidence)); and</div>
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    <div>&#160;</div>
    <table id="zdaa59e79a0454db1b1f4de9fc8e10398" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
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            <div>each Party will promptly notify the other Party of any misuse or unauthorized disclosure of the other Party&#8217;s Confidential Information.</div>
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    <div>&#160;</div>
    <table id="z0580daab10c641ba897b5a9aae33f9a5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The confidentiality, non-use, and non-disclosure obligations set forth in this <u>Section 12.1</u> (Duty of Confidence) will be in full force and effect from the Effective Date until [***] after expiration or termination of this
              Agreement, <font style="font-style: italic;">provided</font> that, with respect to any Know-How that is a trade secret and is identified as such by the Disclosing Party at the time of disclosure, the obligations of this <u>Section 12.1</u>
              (Duty of Confidence) will continue for so long as such Know-How remains a trade secret.</div>
          </td>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.2</td>
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            <div><font style="font-weight: bold;">Confidential Information</font>. Notwithstanding anything to the contrary in the definition of &#8220;Confidential Information&#8221; set forth in <u>Appendix 1</u> (Definitions), the Ionis Product-Specific Know-How,
              any ROFN Exercise Notice, the Joint Collaboration Know-How and the terms of this Agreement will be the Confidential Information of both Parties, with each Party deemed to be the Receiving Party of such information; <font style="font-style: italic;">provided</font> that Ionis Product-Specific Know-How will be deemed the Confidential Information of Ionis following any termination (but not expiration) of this Agreement. The Ionis Core Technology Know-How and the Ionis
              Manufacturing and Analytical Know-How will be the Confidential Information of Ionis. The Otsuka Know-How will be the Confidential Information of Otsuka. Except as provided in <u>Section 12.4</u> (Authorized Disclosures) and <u>Section 12.6</u>
              (Publicity; Use of Names), neither Party nor its Affiliates may disclose the existence or the terms of this Agreement.</div>
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    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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        <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Exemptions</font>. Information of a Disclosing Party will not be Confidential Information of such Disclosing Party to the extent that the Receiving Party can demonstrate through competent evidence that such
              information:</div>
          </td>
        </tr>

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    <div>&#160;</div>
    <table id="z5d9921626529458abe93a5f8e1756d04" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>was already known by the Receiving Party or any of its Affiliates without an obligation of confidentiality at the time of its receipt from the Disclosing Party, and not through a prior disclosure by or on behalf of the Disclosing Party, as
              documented by the Receiving Party&#8217;s business records;</div>
          </td>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>was generally available to the public or otherwise part of the public domain before its receipt from the Disclosing Party;</div>
          </td>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">12.3.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>became generally available to the public or otherwise part of the public domain after its disclosure by the Disclosing Party other than through any act or omission of the Receiving Party or any of its Affiliates or disclosees in breach of
              this Agreement;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z4dc40fdba5e848808b4d6ee9c8b1122d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>is subsequently disclosed to the Receiving Party or any of its Affiliates without obligation of confidentiality by a Third Party who may rightfully do so and is not under a conflicting obligation of confidentiality to the Disclosing Party;
              or</div>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: 39.6pt; vertical-align: top;">12.3.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>is developed by the Receiving Party or any of its Affiliates independently and without use of or reference to any Confidential Information received from the Disclosing Party, as documented by the Receiving Party&#8217;s business records.</div>
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        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 36pt;">No combination of features or disclosures will be deemed to fall within the foregoing exclusions merely because individual features are published or available to the general public or in the rightful
      possession of the Receiving Party unless the combination itself and principle of operation are published or available to the general public or in the rightful possession of the Receiving Party.</div>
    <div>&#160;</div>
    <table id="z71299d6705204593af9b531543363615" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Authorized Disclosures</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z73985053a23643d5957d0e737200f682" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">12.4.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Permitted Circumstances</font>. Notwithstanding the obligations set forth in <u>Section 12.1</u> (Duty of Confidence), a Party may disclose the other Party&#8217;s Confidential Information (including this
              Agreement and the terms herein) to the extent such disclosure is reasonably necessary in the following situations:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z12f11b2a07664dde821021c44bd873e6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
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          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the prosecution or enforcement of Ionis Patent Rights, Collaboration Patent Rights, or Otsuka Patent Rights, in each case, as contemplated by this Agreement;</div>
          </td>
        </tr>

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    <div>&#160;</div>
    <table id="zfceaac4e3e3f489b92c6bf5d8adb79fe" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Regulatory Submissions and other filings or communications with Governmental Authorities (including Regulatory Authorities), as necessary for the Exploitation of the Licensed Products in connection with the exercise of the rights and the
              performance of the obligations of the applicable Party under this Agreement;</div>
          </td>
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    <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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">53</font></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;" noshade="noshade"></div>
    </div>
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        <tr>
          <td style="width: 75.6pt;"><br>
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          <td style="width: 36pt; vertical-align: top;">(c)</td>
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            <div>disclosure of this Agreement, its terms, and the status and results of Exploitation of the Licensed Products to actual or <font style="font-style: italic;">bona fide</font> potential investors, acquirors, (sub)licensees (including any
              counterparty to a Collaboration In-License), lenders, and other financial or commercial partners (including in connection with any royalty financing transaction), and their respective attorneys, accountants, banks, investors, and advisors,
              solely for the purpose of evaluating or carrying out an actual or <font style="font-style: italic;">bona fide</font> potential investment, acquisition, (sub)license, debt transaction, or collaboration transaction; <font style="font-style: italic;">provided </font>that,<font style="font-style: italic;">&#160;</font>in each such case, (i) such Persons are bound by obligations of confidentiality and non-use, or subject to professional ethical obligations of confidentiality, at
              least as stringent as those set forth <u>Article 12</u> (Confidentiality), except that the term of such obligation will be customary for such recipient of Confidential Information and such type of transaction and (ii) the scope of any such
              disclosure is limited to the maximum extent practicable for the particular context in which it is being disclosed;</div>
          </td>
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    </table>
    <div>&#160;</div>
    <table id="z07b1c54434004269ae8c57d2e643008a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>such disclosure is required 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 reasonable discretion. Confidential Information that is disclosed in order to comply with Applicable Law or by judicial or administrative process pursuant to this <u>Section
                12.4.1(d)</u> (Permitted Circumstances), in each case, will remain otherwise subject to the confidentiality and non-use provisions of this <u>Article 12</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 to the maximum 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 12.4.1(d)</u> (Permitted
              Circumstances); or</div>
          </td>
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    </table>
    <div>&#160;</div>
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            <div>disclosure pursuant to <u>Section 12.6</u> (Publicity; Use of Names).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
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          <td style="width: 36pt; vertical-align: top;">(f)</td>
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            <div>If and whenever any Confidential Information is disclosed in accordance with this <u>Section 12.4</u> (Authorized 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>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z236d53196540467fb0c77ea16781ddd4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.5</td>
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            <div><font style="font-weight: bold;">Publications</font>.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">54</font></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;" noshade="noshade"></div>
    </div>
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        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: 39.6pt; vertical-align: top;">12.5.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Otsuka&#8217;s Right to Publish</font>. Otsuka will have the right to publicly present or publish any Clinical Trial data, non-clinical or preclinical data, or any associated results or conclusions generated by
              or on behalf of Ionis or Otsuka pursuant to this Agreement (each such proposed presentation or publication, an &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Publication</font>&#8221;), [***]. If Otsuka desires to publicly present or
              publish an Otsuka Publication in accordance with the foregoing sentence, then Otsuka will provide Ionis (including Ionis&#8217; Alliance Manager and all Ionis members of the JSC) with a copy of such proposed Otsuka Publication at least [***] prior
              to the earlier of its presentation or intended submission for publication (such applicable period, the &#8220;<font style="font-weight: bold; font-style: italic;">Review Period</font>&#8221;). [***]. Notwithstanding any provision to contrary set forth in
              this Agreement, Otsuka will [***]. Otsuka will provide Ionis a copy of any Otsuka Publication at the time of the submission or presentation thereof. Otsuka agrees to determine the authorship of all Otsuka Publications in accordance with all
              applicable International Committee of Medical Journal Editors (ICMJE) guidelines. Otsuka will require its Affiliates and Sublicensees to comply with the obligations of this <u>Section 12.5</u> (Publications) as if they were Otsuka, and
              Otsuka will be liable for any non-compliance of such Persons.</div>
          </td>
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    </table>
    <div>&#160;</div>
    <table id="z635f98ef5a4343e5875050e0f92c35e6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
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            <div><font style="font-weight: bold;">Ionis&#8217; Right to Publish</font>. Ionis will have the right to publicly present or publish any Clinical Trial data, non-clinical or preclinical data, or any associated results or conclusions generated by or
              on behalf of Ionis pursuant to this Agreement (each such proposed presentation or publication, a &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Publication</font>&#8221;) [***]. If Ionis desires to publicly present or publish a Ionis
              Publication in accordance with the foregoing sentence, then Ionis will provide Otsuka (including Otsuka&#8217;s Alliance Manager and all Otsuka members of the JSC) with a copy of such proposed Ionis Publication for review during the applicable
              Review Period. Ionis [***]. Notwithstanding any provision to contrary set forth in this Agreement, Ionis will [***]. Ionis will provide Otsuka a copy of any Ionis Publication at the time of the submission or presentation thereof. Ionis agrees
              to determine the authorship of all Ionis Publications in accordance with all applicable International Committee of Medical Journal Editors (ICMJE) guidelines. Ionis will require its Affiliates to comply with the obligations of this <u>Section
                12.5</u> (Publications) as if they were Ionis, and Ionis will be liable for any non-compliance of such Persons.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">12.5.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Subsequent Publications</font>. After any Otsuka Publication or Ionis Publication has been published or publicly presented in accordance with <u>Section 12.5.1</u> (Otsuka&#8217;s Right to Publish) or <u>Section
                12.5.2</u> (Ionis&#8217; Right to Publish), as applicable, either Party may make subsequent publications or presentations of the content of such previously published Otsuka Publication or Ionis Publication without further approval or review by
              the other Party; <font style="font-style: italic;">provided</font>, that such subsequent publication or presentation does not include any new data, information or conclusions, or present the content in a form or manner that materially alters
              the conclusion or subject matter of the previous publication or public presentation.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Publicity; Use of Names</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z2930f53f8e5845389b8f457d85a275e3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">12.6.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Press Release</font>. The Parties may issue a press release announcing this Agreement, on such date and time and in such form, in each case, as may be agreed by the Parties.<font style="font-weight: bold; font-style: italic;">&#160;</font>Other than such press release and the public disclosures permitted by this <u>Section 12.6.1</u> (Publicity) and <u>Section 12.4</u> (Authorized Disclosures), the Parties agree that the portions of any other
              news release or other public announcement relating to this Agreement or the performance hereunder that would disclose information other than that already in the public domain will require prior review and approval by both Parties (with such
              approval not to be unreasonably withheld, conditioned, or delayed). However, the Parties agree that after (a) a disclosure pursuant to <u>Section 12.6</u> (Publicity; Use of Names) or <u>Section 12.4</u> (Authorized Disclosures) or (b) the
              issuance of a press release (including the initial press release) or other public announcement pursuant to this <u>Section 12.6.1</u> (Press Release) that has been reviewed and approved by the other Party, the disclosing 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 such
              disclosure is consistent with prior disclosures approved by the other Party pursuant to this <u>Section 12.6</u> (Publicity; Use of Names) and which do not reveal non&#8209;public information about the other Party. Similarly, after a Publication
              has been made available to the public, each Party may post such Publication or a link to it on its corporate website or social media platforms (or any website managed by such Party in connection with a Clinical Trial for the Licensed
              Products, as appropriate) without the prior written consent of the other Party, so long as the information in such Publication remains true, correct, and the most current information with respect to the subject matters set forth therein.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">55</font></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;" noshade="noshade"></div>
    </div>
    <table id="z8a062e2c7fd14dbd9048bdc875ee0088" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">12.6.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Disclosures by Ionis</font>. Notwithstanding any provision to the contrary set forth in this Agreement, Ionis has the right to publicly disclose (in written, oral, or other form): (a) the achievement of any
              Regulatory Milestone Event or Sales Milestone Event under this Agreement (including the timing of achievement of any such milestone event but without disclosing the amount of such milestone payment unless permitted pursuant to <u>Section
                12.4.1(d)</u> (Permitted Circumstances)); (b) the commencement, completion, material data, or key results of any Clinical Trials for the Licensed Products conducted by or on behalf of Ionis; and (c) the achievement of Regulatory Approval
              for any Licensed Product throughout the world; <font style="font-style: italic;">provided </font>that,<font style="font-style: italic;">&#160;</font>subject to <u>Section 12.4.1(d)</u> (Permitted Circumstances), [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z8a8b94bf40684bf7a8e971615a1b177c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">12.6.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Use of Names</font>. Each Party will have the right to use the other Party&#8217;s name and logo in presentations, its website, collateral materials, and corporate overviews to describe the collaboration
              relationship, as well as in taglines of press releases issued pursuant to this <u>Section 12.6</u> (Publicity; Use of Names); <font style="font-style: italic;">provided </font>that neither Party will [***], and each Party will [***].
              Except as permitted under this <u>Section 12.6</u> (Publicity; Use of Names) or with the prior express written permission of the other Party, neither Party will use the name, trademark, trade name, or logo of the other Party or its
              Affiliates or their respective employees in any publicity, promotion, news release, or disclosure relating to this Agreement or its subject matter except as may be required by Applicable Law.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z78edab81181940f98558e14eb41fc7e7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Acknowledgement</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zef83f50142a243e28491f06856c6d818" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">12.7.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>To the extent permitted under Applicable Law in the Otsuka Territory, Otsuka will acknowledge in any press release, public presentation, or publication regarding a Licensed Product Ionis&#8217; role in discovering and developing the Licensed
              Products, that the Licensed Products are under license from Ionis, and [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z677bbe316bed48c7a4bfc66cc1e523a5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">12.7.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Otsuka agrees that it will acknowledge Ionis&#8217; role in the discovery of a Licensed Product in any scientific, medical, and other Licensed Product-related communications [***], by including the words &#8220;<font style="font-style: italic;">Discovered
                by Ionis</font>&#8221; or equivalent language (collectively, the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Attribution Language</font>&#8221;) in any such communications; <font style="font-style: italic;">provided, however</font>,
              that [***].</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">56</font></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;" noshade="noshade"></div>
    </div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 13</div>
    <div style="text-align: center; font-weight: bold;">INDEMNIFICATION</div>
    <div>&#160;</div>
    <table id="z1363a68592504afebfe9c2c87196ab4f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Indemnification by Ionis</font>. Ionis will indemnify, hold harmless, and defend Otsuka and its Affiliates and their respective directors, officers, employees, and agents (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Indemnitee</font>&#8221;) from and against any and all Third Party suits, claims, actions, or demands (&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Claims</font>&#8221;) and all
              liabilities, expenses, or losses (including reasonable attorneys&#8217; fees, court costs, witness fees, damages, judgments, fines, and amounts paid in settlement) (&#8220;<font style="font-weight: bold; font-style: italic;">Losses</font>&#8221;) arising
              therefrom to the extent that the applicable Third Party Claims and such Losses arise out of (a) a breach of this Agreement by Ionis, (b) the Exploitation of the Licensed Products by or on behalf of Ionis or any of its Affiliates, licensees
              (not including Otsuka or its Affiliates, Sublicensees, or its Subcontractors), Sublicensees, or Subcontractors, or (c) the negligence or willful misconduct of any Ionis Indemnitee. Notwithstanding the foregoing, Ionis will not have any
              obligation to indemnify Otsuka Indemnitees to the extent that any Losses arise out of any Third Party Claim for which Otsuka is responsible for indemnifying Ionis pursuant to <u>Section 13.2</u> (Indemnification by Otsuka).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="ze216fba7a6364949b20f9ac00f396ea7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Indemnification by Otsuka</font>. Otsuka will indemnify, hold harmless, and defend Ionis and its Affiliates, and their respective directors, officers, employees, and agents (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Indemnitee</font>&#8221;) from and against any and all Third Party Claims and all Losses arising therefrom, to the extent that the applicable Third Party Claims and such Losses arise out of (a)
              a breach of this Agreement by Otsuka, (b) the Exploitation of the Licensed Products by or on behalf of Otsuka or any of its Affiliates, Sublicensees, or Subcontractors, or (c) the negligence or willful misconduct of any Otsuka Indemnitee<font style="color: rgb(0, 0, 0);">. </font>Notwithstanding any provision to the contrary set forth in this Agreement,<font style="color: rgb(0, 0, 0);"> Otsuka will not have any obligation to indemnify the Ionis Indemnitees to the extent that
                any&#160;</font>Losses arise out of any Third Party Claim for which Ionis is responsible for indemnifying Otsuka pursuant to <u>Section 13.1</u> (Indemnification by Ionis).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z460d3f8ff4c246dfb90620099c0ab3ee" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Indemnification Procedure</font>. If either Party is seeking indemnification under <u>Section 13.1</u> (Indemnification by Ionis) or <u>Section 13.2</u> (Indemnification by Otsuka) (the &#8220;<font style="font-weight: bold; font-style: italic;">Indemnified Party</font>&#8221;), then it will inform the other Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Indemnifying Party</font>&#8221;) of the Third Party Claim giving rise to
              such indemnification obligations within [***] after receiving written notice of the Third Party Claim (it being understood and agreed, however, that the failure or delay by an Indemnified Party to give such notice of a Third Party Claim will
              not affect the Indemnifying Party&#8217;s indemnification obligations hereunder except to the extent the Indemnifying Party will have been actually prejudiced as a result of such failure or delay to give notice). The Indemnifying Party will have
              the right to assume the defense of any such Third Party Claim for which it is obligated to indemnify the Indemnified Party. The Indemnified Party will cooperate with the Indemnifying Party and the Indemnifying Party&#8217;s insurer as the
              Indemnifying Party may reasonably request, and at the Indemnifying Party&#8217;s cost and expense. The Indemnified Party will have the right to participate, with counsel of its choice, in the defense of any Third Party that has been assumed by the
              Indemnifying Party, which participation will be at the Indemnified Party&#8217;s expense unless (a) the Indemnifying Party has agreed to pay such fees and expenses, or (b) the Indemnified Party has been advised by counsel that there are actual or
              potential conflicting interests between the Indemnifying Party and the Indemnified Party, including situations in which there are one or more legal defenses available to the Indemnified Party that are different from or additional to those
              available to the Indemnifying Party. Neither Party will have the obligation to indemnify the other Party in connection with any settlement made without the Indemnifying Party&#8217;s written consent, which consent will not be unreasonably withheld,
              conditioned, or delayed. The Indemnifying Party will not admit any fault or negligence on the part of the Indemnified Party, or impose any obligation on, or otherwise adversely affect, the Indemnified Party, without the Indemnified Party&#8217;s
              prior written consent, which consent will not be unreasonably withheld, conditioned, or delayed. If the Parties cannot agree as to the application of <u>Section 13.1 </u>(Indemnification by Ionis) or <u>Section 13.2</u> (Indemnification by
              Otsuka) as to any Third Party Claim, then, pending resolution of the dispute pursuant to <u>Article 15</u> (Dispute Resolution; Governing Law), then the Parties may conduct separate defenses of such Third Party Claims, with each Party
              retaining the right to claim indemnification from the other Party in accordance with <u>Section 13.1</u> (Indemnification by Ionis) or <u>Section 13.2</u> (Indemnification by Otsuka), as applicable, upon resolution of the underlying Third
              Party Claim.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">57</font></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;" noshade="noshade"></div>
    </div>
    <table id="z43ed24b9df6541798e8e4e96cc877ff9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Insurance</font>. Each Party will, at its own expense, procure and maintain insurance, including product liability insurance, adequate to cover its obligations hereunder and that is consistent with normal
              business practices of prudent companies similarly situated at all times during which any Licensed Product is being clinically tested in human subjects or commercially distributed or sold by such Party pursuant to this Agreement. It is
              understood that such insurance will not be construed to create a limit of either Party&#8217;s liability with respect to its indemnification obligations under this <u>Article 13</u> (Indemnification). Each Party will provide the other Party with
              written evidence of such insurance upon request. Each Party will provide the other Party with [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 14</div>
    <div style="text-align: center; font-weight: bold;">TERM AND TERMINATION</div>
    <div>&#160;</div>
    <table id="z22298553b21f410d96eb752e13fa4d7e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Term</font>. The term of this Agreement will begin on the Effective Date and, unless earlier terminated in accordance with this <u>Article 14</u> (Term and Termination), will continue until Otsuka, its
              Affiliates, and its Sublicensees are no longer Commercializing any Licensed Product in any country in the Otsuka Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Term</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="za33d8dab4ef24c7ca9620b0a48326222" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Termination for Material Breach</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z948496760d5648d4b67442c5ce14d515" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Material Breach</font>. If either Party believes in good faith that the other is in material breach of this Agreement, then the non-breaching Party may deliver notice of such breach to the other Party
              stating the cause and proposed remedy (&#8220;<font style="font-weight: bold; font-style: italic;">Breach Notification</font>&#8221;). For any breach alleged in any Breach Notification arising from a failure to make a payment set forth in this Agreement,
              the allegedly breaching Party will have [***] from the receipt of the applicable Breach Notification to cure such breach. For all breaches other than a failure to make a payment as set forth in this Agreement, the allegedly breaching Party
              will have [***] from the date of the Breach Notification to cure such breach. If the allegedly breaching Party fails to cure the applicable breach within the applicable period set forth above, then the Party originally delivering the Breach
              Notification may terminate this Agreement effective on written notice of termination to such allegedly breaching Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z17ba6974b45b46728b2b884be4e6d3a2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Disagreement as to Material Breach</font>. Notwithstanding <u>Section 14.2.1</u> (Material Breach), if the Parties, reasonably and in good faith, disagree as to whether there has been a material breach of
              this Agreement, then: (a) the Party that disputes whether there has been a material breach may contest the allegation by referring such matter, within the cure period applicable to such alleged material breach, for resolution in accordance
              with <u>Article 15</u> (Dispute Resolution; Governing Law); (b) the relevant cure period with respect to such alleged material breach will be tolled from the date on which the Party that disputes whether there has been a material breach
              notifies the other Party of such dispute and through the resolution of such dispute in accordance with <u>Article 15</u> (Dispute Resolution; Governing Law); and (c) during the pendency of such dispute, all of the terms and conditions 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 id="zfe14216243b640f9aa9024ef4561d496" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Termination by Otsuka for Convenience</font>. Otsuka will have the right to terminate this Agreement in its entirety at any time during the Term upon (a) [***] and (b) [***].</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">58</font></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;" noshade="noshade"></div>
    </div>
    <table id="z77c2320a8ad842c09875d9a7e7fdc02d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Discontinuation of Development and Commercialization</font>. If Otsuka and its Affiliates and Sublicensees have not conducted any material Development or Commercialization activities with respect to the
              Licensed Products in any country in the Otsuka Territory for a continuous period of [***], and such discontinuation of activity is not: (a) by written agreement of the Parties,&#160;(b) due to [***], or (c) due to a Force Majeure,<font style="font-weight: bold; font-style: italic;">&#160;</font>then Ionis may, at its election, terminate this Agreement in its entirety upon [***] prior written notice to Otsuka. For purposes of this <u>Section 14.4</u> (Discontinuation of
              Development and Commercialization), the use of reasonable efforts, to the extent possible, by Otsuka or its Affiliates or Sublicensees (as applicable) to resolve a Force Majeure, clinical hold or other action or inaction of a Regulatory
              Authority, or any scientific or technical issues, Manufacturing or supply interruption or other material adverse event outside of Otsuka&#8217;s control for the Licensed Product will, in each case, be considered material Development or
              Commercialization activities.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="za4d81fea776c4d76b5527899f1063604" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Termination For Patent Challenge</font>. Except to the extent unenforceable under Applicable Law, Ionis may terminate this Agreement in its entirety upon [***] prior written notice of termination to Otsuka
              if Otsuka or its Affiliates or Sublicensees (individually or in association with any Person) commences or assists a Third Party in commencing or conducting a Patent Challenge with respect to any Ionis Patent Right, <font style="font-style: italic;">provided</font> that, Ionis shall not have the right to terminate this Agreement on account of such Patent Challenge (a) if, within [***] after receipt by Otsuka of the written notice from Ionis as set forth above in this <u>Section
                14.5</u> (Termination for Patent Challenge), Otsuka or its Affiliate, as applicable, rescinds such Patent Challenge (or in the case of any ex-parte proceeding, multi-party proceeding, or other Patent Challenge that Otsuka or such Affiliate
              does not have the power to unilaterally withdraw or cause to be withdrawn, Otsuka and its Affiliate, as applicable, knowingly ceases providing any direction to any Person with respect to such Patent Challenge and, to the extent Otsuka or any
              of its Affiliates is a party to such Patent Challenge and to the extent permitted by the applicable tribunal, it withdraws from such Patent Challenge) and <font style="font-style: italic;">provided</font> that neither Otsuka nor any of its
              Affiliates thereafter continues such Patent Challenge or, knowingly provides any direction to any Person in respect of the same or (b) in the case of any Patent Challenge commenced by a Sublicensee of Otsuka or its Affiliate, if Otsuka or its
              Affiliate, as applicable, terminates such Sublicensee&#8217;s sublicense under any Ionis Technology within [***] after receipt by Otsuka of the applicable written notice from Ionis as set forth above in this <u>Section 14.5</u> (Termination for
              Patent Challenge). If Ionis has the right to terminate this Agreement in accordance with this <u>Section 14.5</u> (Termination for Patent Challenge) but such termination is prohibited under Applicable Law, then in lieu of such termination,
              [***]. If Ionis [***], then [***]. Notwithstanding the foregoing, Ionis shall not have the right to terminate this Agreement pursuant to this <u>Section 14.5</u> (Termination for Patent Challenge) if Otsuka or any of its Affiliates or its or
              their Sublicensees commences a Patent Challenge (i) in a proceeding involving an Ionis Patent Right in which Otsuka or any of its Affiliates or its or their Sublicensees has been compelled to participate in the proceeding by a court, patent
              office, or Third Party or (ii) that is necessary or reasonably required to assert a cross-claim or a counterclaim or to respond to a court request or order or administrative law request or order, including asserting any defense or
              counterclaim in, or otherwise responding to, an action for infringement of intellectual property asserted, filed or threatened to be filed against Otsuka or any of its Affiliates or its or their Sublicensees by Ionis or any of its Affiliates
              or its or their Sublicensees.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Termination for Insolvency</font>. Each Party will have the right to terminate this Agreement upon delivery of written notice to the other Party if (a) such other Party files in any court or agency pursuant
              to any statute or regulation of any jurisdiction a petition in bankruptcy or insolvency or for reorganization or similar arrangement for the benefit of creditors or for the appointment of a receiver or trustee of such other Party or its
              assets, (b) such other Party is served with an involuntary petition against it in any insolvency proceeding and such involuntary petition has not been stayed or dismissed within [***] of its filing, or (c) such other Party makes an assignment
              of substantially all of its assets for the benefit of its creditors.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">59</font></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;" noshade="noshade"></div>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Rights in Bankruptcy</font>. The Parties intend to take advantage of the protections of Section 365(n) (or any successor provision) of the U.S. Bankruptcy Code or any analogous provisions in any other
              country or jurisdiction to the maximum extent permitted by Applicable Law. All rights and licenses granted under or pursuant to this Agreement shall be deemed to be &#8220;intellectual property&#8221; for the purposes of Section 365(n) or any analogous
              provisions in any other country or jurisdiction. The Parties shall retain and may fully exercise all of their rights and elections under the U.S. Bankruptcy Code or any analogous provisions in any other country or jurisdiction, including the
              right to obtain the intellectual property from another entity. In the event of the commencement of a bankruptcy proceeding by or against either Party under the U.S. Bankruptcy Code or any analogous provisions in any other country or
              jurisdiction, the Party that is not subject to such proceeding shall be entitled to a complete duplicate of (or complete access to, as appropriate) all such intellectual property (including all embodiments of such intellectual property),
              which, if not already in the non-subject Party&#8217;s possession, shall be promptly delivered to it upon the non-subject Party&#8217;s written request (a) upon commencement of a bankruptcy proceeding, unless the Party subject to such proceeding
              continues to perform all of its obligations under this Agreement, or (b) if not delivered pursuant to clause (a) above because the subject Party continues to perform, upon the rejection of this Agreement by or on behalf of the subject Party.
              Unless and until the subject Party rejects this Agreement, the subject Party shall perform this Agreement or provide the intellectual property (including all embodiments of such intellectual property) to the non-subject Party, and shall not
              interfere with the rights of the non-subject Party to such intellectual property, including the right to obtain the intellectual property from another entity.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Full Force and Effect During Notice Period</font>. This Agreement will remain in full force and effect until the expiration of the applicable termination notice period. For clarity, if Otsuka or any of its
              Affiliates or Sublicensees achieve any Milestone Events during the termination notice period, then the corresponding Milestone Payment is accrued and Otsuka will remain responsible for the payment of such Milestone Payment even if the due
              date of such Milestone Payment occurs after the effective date of the termination.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z10abeb8c6e0a48a1b12471283cc620f6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Effects of Termination</font>. If this Agreement is terminated by either Party pursuant to <u>Section 14.2</u> (Termination for Material Breach) or <u>Section 14.6</u> (Termination for Insolvency), by
              Otsuka pursuant to <u>Section 14.3</u> (Termination by Otsuka for Convenience), or by Ionis pursuant to <u>Section 14.4</u> (Discontinuation of Development and Commercialization), or <u>Section 14.5</u> (Termination for Patent Challenge),
              then all rights in the Licensed Products will revert to Ionis, and the following will apply with respect to the Licensed Products:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.9.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Termination of Licenses</font>. As of the effective date of termination of this Agreement, all rights licensed to Otsuka under <u>Section 2.1</u> (License Grants to Otsuka) or otherwise under this
              Agreement (except for the licenses granted under <u>Section 2.4</u> (Collaboration Technology Enabling License)), in each case, will each terminate, but each Party will retain its joint ownership interests in the Joint Collaboration
              Technology.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.9.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Reversion License</font>.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">60</font></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;" noshade="noshade"></div>
    </div>
    <table id="z0d7a873ffc56408a99e0c42069f2c209" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">License Grant</font>. Ionis will have, and Otsuka hereby grants to Ionis, effective upon such termination, a worldwide, [***] license under any Patent Rights and Know-How Controlled by Otsuka as of the
              effective date of such termination, other than any Otsuka Technology, that, in each case, are used by Otsuka or its Affiliates in the Exploitation of any Licensed Product prior to or as of the effective date of such termination solely to
              Exploit the Licensed Products in the Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Reversion License</font>&#8221;). Except as otherwise provided in <u>Section 14.9.8</u> (Sell-Off), Otsuka will not have the right to
              Commercialize any Licensed Product in the Territory upon and following the effective date of termination of this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zca57820011ec42bd8a3091ff7d42cd3f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Reversion Royalty</font>. Ionis will pay, on a Calendar Quarter basis during the applicable Royalty Term (defined <font style="font-style: italic;">mutatis mutandis</font> with respect to the Reversion
              License except that, for clarity, references to the Ionis Patent Rights in such definition will instead refer to any Patent Rights licensed by Otsuka to Ionis under the Reversion License) a [***] royalty on Ionis&#8217; Net Sales (defined <font style="font-style: italic;">mutatis mutandis</font> with respect to the Reversion License) of each Licensed Product in the Territory. The provisions of <u>Section 9.3.4</u> (Royalty Payments and Reports)&#160; through <u>Section 9.11</u> (Late
              Payments; Disputed Payments) will apply to such payment obligation <font style="font-style: italic;">mutatis mutandis. </font>Notwithstanding the foregoing, in no event will the total amount of the reversion royalty payments under this <u>Section

                14.9.2(b)</u> (Reversion Royalty) exceed [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z2aadbeb03e1f4d10bd5f11f34e5c0954" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.9.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Transition Services</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zfb6285be8f3f4a3f83b916578223d3ab" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Scope</font>. Ionis may request that Otsuka perform transition activities with respect to any Licensed Products in the Otsuka Territory that are necessary to transition the responsibilities under all
              Regulatory Approvals and ongoing Clinical Trials for Licensed Products to Ionis or its designee. If Ionis requests that Otsuka perform any such transition activities, then the Parties will enter into a transition agreement containing a plan
              for Otsuka to perform the transition services listed in <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 14.9.3</u> (Transition Services), to the extent applicable at the time of termination, and such other transition
              services that the Parties mutually agree to (such plan, the &#8220;<font style="font-weight: bold; font-style: italic;">Transition Plan</font>&#8221; and such activities, the &#8220;<font style="font-weight: bold; font-style: italic;">Transition Services</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z041b0b93f9494cdca45384ae227d8e21" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Transition Plan</font>. Ionis may elect to have Otsuka perform the Transition Services by providing written notice to Otsuka no later than [***] following the effective date of the termination. If Ionis
              requests that Otsuka perform the Transition Services, then Ionis will propose a draft of the Transition Plan setting forth the Transition Services to be performed by Otsuka and the Parties will negotiate and enter into the Transition Plan,
              which will be consistent with this <u>Section 14.9.3</u> (Transition Services) and will include, to the extent applicable, the services listed on <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 14.9.3</u> (Transition
              Services), within [***] after such request. In addition, the Parties will, within [***] after such request, establish a transition committee consisting of at least each Party&#8217;s Alliance Managers, a representative from each Party&#8217;s CMC group
              who was responsible for the Licensed Product prior to the termination, and up to two additional representatives from each Party who are from other relevant functional groups to facilitate a smooth transition. While Otsuka is providing
              Transition Services, Otsuka and Ionis will mutually agree on talking points and a communication plan to customers, specialty pharmacies, physicians, Regulatory Authorities, patient advocacy groups, and clinical study investigators, and Otsuka
              will make all such communication to such entities in accordance with the mutually agreed talking points.</div>
          </td>
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    <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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">61</font></div>
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        <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
    </div>
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          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Costs</font>. Ionis will pay Otsuka for [***]. In addition, Ionis will reimburse Otsuka for [***]. Otsuka will submit an invoice, together with supporting documentation of [***], to Ionis quarterly for the
              foregoing costs incurred by or on behalf of Otsuka in such Calendar Quarter, and Ionis will pay the undisputed invoiced amounts within [***] after the date of such invoice (and will pay any disputed amounts within [***] following resolution
              of the dispute and determination that such amounts are owed).</div>
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    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.9.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Return of Confidential Information</font>. Each Party will return or destroy (at the other Party&#8217;s election) all Confidential Information of the other Party in its possession upon termination of this
              Agreement and, if applicable, the Receiving Party will provide a written confirmation of such destruction within [***] of such request. Notwithstanding the foregoing or any provision to the contrary set forth in this Agreement: (a) the
              foregoing terms of this <u>Section 14.9.4</u> (Return of Confidential Information) will not apply to any Confidential Information that is necessary to allow the Receiving Party to perform its obligations or exercise any of its rights that
              expressly survive the applicable termination of this Agreement, and the Receiving Party may retain one copy of such Confidential Information for its legal archives; and (b) the Receiving Party will not be required to destroy electronic files
              containing such Confidential Information that are made in the ordinary course of its business information back-up procedures pursuant to its electronic record retention and destruction practices that apply to its own general electronic files
              and information.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zf561094882184fa6811f9f714e5b7ffd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: 39.6pt; vertical-align: top;">14.9.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Sublicenses</font>. If this Agreement is terminated prior to expiration, then Ionis shall grant to each Sublicensee of Otsuka, at each such Sublicensee&#8217;s written request to Ionis within [***] of the
              effective date of termination, a direct license, <font style="font-style: italic;">provided</font> that such Sublicensee (a) is not then in default of its sublicense agreement or this Agreement, (b) agrees in writing to comply with the terms
              of this Agreement to the extent applicable to the rights originally sublicensed to such Sublicensee by Otsuka, and (c) agrees to pay directly to Ionis such Sublicensee&#8217;s payments under such sublicense agreement. The scope of such direct
              license shall be no less than the scope of the license granted herein and sublicensed to such Sublicensee, and Ionis shall have no obligation to perform any task for such Sublicensee beyond the obligations owed to Otsuka hereunder. Each
              Sublicensee will be an intended Third Party beneficiary of this <u>Section 14.9.5</u> (Sublicenses) with the right to enforce the same against Ionis.</div>
          </td>
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    </table>
    <div>&#160;</div>
    <table id="z6192d76a8af940259a8624c72f279367" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: 39.6pt; vertical-align: top;">14.9.6</td>
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            <div><font style="font-weight: bold;">Assignment</font>. To the extent requested by Ionis in writing following the date that a Party provides notice of termination of this Agreement, Otsuka will promptly (and in any event no later than [***]
              after the effective date of termination unless agreed otherwise in the Transition Plan or expressly specified otherwise below):</div>
          </td>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>provide to Ionis for its review unredacted copies of all clinical trial agreements and distribution agreements (to the extent assignable, not cancelled, and solely related to the Licensed Products), in each case, that are necessary or
              reasonably useful for the Exploitation of the Licensed Products, and, following such review, upon Ionis&#8217; written request within [***] after entering into a Transition Plan or [***] after the effective date of termination if Ionis does not
              elect to enter into a Transition Plan, assign and transfer to Ionis or its designee all of Otsuka&#8217;s rights, title, and interests in and to any such agreements;</div>
          </td>
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    </table>
    <div>&#160;</div>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>assign to Ionis any Potential In-Licenses entered into by Otsuka pursuant to <u>Section 2.7.2</u> (Potential In-Licenses);</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">62</font></div>
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        <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
    </div>
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        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>assign any agreements or arrangements with Third Party vendors (including distributors) solely related to the Licensed Products or, to the extent any such Third Party agreement or arrangement is not assignable to Ionis, reasonably
              cooperate with Ionis to arrange to continue to provide such services for a reasonable time after termination of this Agreement to facilitate the orderly transition of all Commercialization and other activities then being performed by or on
              behalf of Otsuka or its Affiliates or Sublicensees for the Licensed Products to Ionis or its designee;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z17f515c9c07341ce9d89800730930a1a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>assign and transfer to Ionis or its designee, as of the effective date of termination, all of Otsuka&#8217;s rights, title, and interests in and to the Otsuka Product Trademarks and any domain names associated with the Otsuka Product Trademarks
              (to the extent that Otsuka or its Affiliates has any) and promptly provide to Ionis all information necessary to maintain such domain names;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="ze0e3cfaee07b4209ab7eaedd63d6af33" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(e)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>assign and transfer to Ionis or its designee, as of the effective date of termination, all of Otsuka&#8217;s rights, title, and interests in and to any Product Materials specifically related to the Licensed Products,<font style="font-weight: bold; font-style: italic;">&#160;</font>and copyrights and any registrations for the foregoing (to the extent that Otsuka or its Affiliates has any); and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z615b284d06ba479c94ddacc5081a4055" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 75.6pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(f)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>within [***] after entering into a Transition Plan or [***] after the effective date of termination if Ionis does not elect to enter into a Transition Plan, disclose to Ionis or its designee all documents, records, and materials that
              embody any of the foregoing and that are Controlled by Otsuka.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 75.6pt;">To the extent that any agreement or other asset described in this <u>Section 14.9.6 </u>(Assignment) is not assignable by Otsuka, then such agreement or other asset will not be assigned, and upon
      the request of Ionis, Otsuka will take such steps as may be necessary to allow Ionis to obtain and to enjoy the benefits of such agreement or other asset, in the form of a license or other right to the extent Otsuka has the right and ability to do
      so; <font style="font-style: italic;">provided</font> that such steps will not require Otsuka to [***] in order to obtain and enjoy such benefits. For clarity, Ionis will have the right to request that Otsuka take any or all of the foregoing actions
      in whole or in part, or with respect to all or any portion of the assets set forth in the foregoing provisions.</div>
    <div>&#160;</div>
    <table id="zf940eb821a214f9993ee363d7816ac71" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.9.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Regulatory Submissions and Regulatory Approvals</font>. Otsuka will and hereby does, and will cause its Affiliates and Sublicensees to, (a) no later than [***] after the effective date of termination of
              this Agreement, assign and transfer to Ionis or its designee all of Otsuka&#8217;s rights, title, and interests in and to all Regulatory Submissions, Regulatory Approvals, and Reimbursement Approvals solely for the Licensed Products then Controlled
              by Otsuka or any of its Affiliates or Sublicensees (for any Sublicensees that do not become a direct licensee of Ionis pursuant to <u>Section 14.9.5</u> (Sublicenses)), and (b) to the extent assignment pursuant to clause (a) is delayed or is
              not permitted by the applicable Regulatory Authority, permit Ionis to cross-reference and rely upon any such Regulatory Submissions, Regulatory Approvals, and Reimbursement Approvals filed by Otsuka or any of its Affiliates or Sublicensees
              (for any Sublicensees that do not become a direct licensee of Ionis pursuant to <u>Section 14.9.5</u> (Sublicenses)). Otsuka will execute and deliver, or will cause to be executed and delivered, to Ionis or its designee such endorsements,
              assignments, commitments, acknowledgements, and other documents as may be necessary to effect the foregoing assignment, including submitting to each applicable Regulatory Authority or other Governmental Authority a letter or other necessary
              documentation (with copy to Ionis) notifying such Regulatory Authority or other Governmental Authority of, or otherwise giving effect to, the transfer of ownership to Ionis of all such assigned Regulatory Submissions, Regulatory Approvals,
              and Reimbursement Approvals. In addition, upon Ionis&#8217; written request, Otsuka will, [***] (other than in the event of termination of this Agreement by Otsuka pursuant to <u>Section 14.2</u> (Termination for Material Breach) or <u>Section
                14.6</u> (Termination for Insolvency), in which case Ionis shall [***]), provide to Ionis copies of all material related documentation, including material non-clinical, preclinical, and clinical data related to the Licensed Products that
              are held by or reasonably available to Otsuka or its Affiliates or Sublicensees (for any Sublicensees that do not become a direct licensee of Ionis pursuant to <u>Section 14.9.5</u> (Sublicenses)).</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">63</font></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;" noshade="noshade"></div>
    </div>
    <table id="z382019ab6c3d4abfb1307cf8f7e59ec4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.9.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Sell-Off</font>. If Otsuka is Commercializing any Licensed Product in any country in the Otsuka Territory as of the applicable effective date of termination, then, [***], either (a) Otsuka will appoint
              Ionis or its designee as its exclusive distributor of such Licensed Product in such country and grant Ionis or its designee the right to appoint sub-distributors, to the extent not prohibited by any written agreement between Otsuka or any of
              its Affiliates and a Third Party or (b) Otsuka will have the continued right to sell the Licensed Products in the Otsuka Territory from its inventory; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>,
              that Otsuka&#8217;s obligations under this Agreement with respect to the Licensed Products that Otsuka sells, including the obligation to pay Royalties to Ionis hereunder, will continue in full force and effect during such period. If Ionis elects
              to be appointed as the exclusive distributor pursuant to the foregoing clause (a), then the Parties will enter into a distribution agreement with respect to such appointment and Ionis will use good faith efforts to distribute such Licensed
              Product in such country, or otherwise distribute such Licensed Product in such country, in accordance with the terms of the distribution agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z2c8276c02b844908a9d0f4811bdae3be" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.9.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Inventory</font>. [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z4397bae4e9774cb59c2ad082fb801c69" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.9.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Wind Down and Transition</font>. Otsuka will be responsible, [***] (other than in the event of termination of this Agreement by Otsuka pursuant to <u>Section 14.2</u> (Termination for Material Breach) or <u>Section
                14.6</u> (Termination for Insolvency), in which case Ionis shall [***]), for the wind-down of Otsuka&#8217;s and its Affiliates&#8217; and Sublicensees (for any Sublicensees that do not become a direct licensee of Ionis pursuant to <u>Section 14.9.5</u>
              (Sublicenses)) activities with respect to the Licensed Products. Otsuka will, and will cause its Affiliates and such Sublicensees to, reasonably cooperate with Ionis to facilitate orderly transition to Ionis or its designee of all
              Commercialization and other activities then being performed by or on behalf of Otsuka or its Affiliates for the Licensed Products in the Otsuka Territory.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zb0ddb7d24f0d4ca7969a0718c7380313" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.9.11</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cost of Transition Activities</font>. Notwithstanding any provision to the contrary in this <u>Section 14.9</u> (Effects of Termination), but without limiting <u>Section 14.9.3(c)</u> (Costs), if Otsuka
              terminates this Agreement pursuant to <u>Section 14.2</u> (Termination for Material Breach) or <u>Section 14.6</u> (Termination for Insolvency), Ionis will be responsible for, and will pay Otsuka, [***]. Otsuka will submit an invoice,
              together with supporting documentation of [***], to Ionis quarterly for the foregoing costs incurred by or on behalf of Otsuka in such Calendar Quarter, and Ionis will pay the undisputed invoiced amounts within [***] after the date of any
              such invoice (and will pay any disputed amounts within [***] following resolution of the dispute and determination that such amounts are owed).</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">64</font></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;" noshade="noshade"></div>
    </div>
    <table id="z563bb85efddb4df5a9f78bf9a4da4307" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">14.9.12</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Other Assistance; Further Assurances</font>. Otsuka will provide any other assistance reasonably requested by Ionis for the purpose of allowing Ionis or its designee to proceed expeditiously with the
              Exploitation of the Licensed Products for a period of [***] after the effective date of termination of this Agreement. Otsuka will execute all documents, and take all such further actions as may be reasonably requested by Ionis in order to
              give effect to the requirements in this <u>Section 14.9</u> (Effects of Termination).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zf848245924794aa6a3a25f383731aed0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Survival; Accrued Rights</font>. Expiration or termination of this Agreement will not relieve the Parties of any liability that accrued hereunder prior to the effective date of such expiration or
              termination nor 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 either Party&#8217;s right to obtain performance of any obligation.
              Without limiting the foregoing, the following provisions of this Agreement will survive the expiration or termination of this Agreement: <u>Section 2.2</u> (License Grant to Ionis); <u>Section 2.4</u> (Collaboration Technology Enabling
              License); <u>Section 4.6</u> (Development Records; Cooperation) (solely with respect to the obligation to maintain records for at least [***] after the end of the Term or for such longer period as may be required by Applicable Law); <u>Article
                9</u> (Payments) (solely with respect to amounts that accrued prior to the effective date of termination and, with respect to <u>Section 9.5</u> (Financial Records and Audits), solely for [***] after the effective date of termination), <u>Section
                10.1</u> (Inventions); <u>Section 11.5</u> (Disclaimer); <u>Section 11.6</u> (Limitation of Liability); <u>Article 12</u> (Confidentiality, excluding <u>Section 12.5</u> (Publications)); <u>Article 13</u> (Indemnification); <u>Section
                14.9 </u>(Effects of Termination); this S<u>ection 14.10</u> (Survival; Accrued Rights); <u>Article 15</u> (Dispute Resolution; Governing Law); <u>Article 16</u> (Miscellaneous); and <u>Appendix 1</u> (Definitions).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 15</div>
    <div style="text-align: center; font-weight: bold;">DISPUTE RESOLUTION; GOVERNING LAW</div>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Executive Officers; Disputes</font>. Each Party will ensure that an Executive Officer is designated for such Party at all times during the Term for dispute resolution purposes, and will promptly notify the
              other Party of any change in its designated Executive Officer. In the event of a dispute, controversy or claim arising under, relating to, or in connection with this Agreement (except for disputes arising at the JSC, which will be resolved in
              accordance with <u>Section </u><u>8.4</u> (Decision-Making) and <u>Section 8.5</u> (Resolution of Committee Disputes)) (a &#8220;<font style="font-weight: bold; font-style: italic;">Disputed Matter</font>&#8221;), then the Parties will refer such
              dispute to their respective Executive Officer, and such Executive Officers or designees will attempt in good faith to resolve such dispute. If the Parties are unable to resolve any such dispute within [***] after both Parties have referred
              such dispute to their designated Executive Officers pursuant to this <u>Section 15.1</u> (Executive Officers; Disputes), then either Party will have the right to pursue any and all remedies available at law or equity, as set forth in <u>Section
                15.2</u> (Arbitration) or <u>Section 15.3</u> (Intellectual Property Disputes), as applicable.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd60b5e1d77a34f6f9f93f79cd4f27084" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Arbitration</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z4ac6ed65ce1d4bf18d4eae4470c13a94" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">15.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="color: rgb(0, 0, 0);">If the Parties are unable to resolve a Disputed Matter using the process described in <u>Section 15.1</u> (Executive Officers; Disputes) and <u>Section 15.3</u> (Intellectual Property Disputes) does not
                apply, then a Party seeking further resolution of the Disputed Matter will submit the Disputed Matter to resolution by final and binding arbitration in accordance with this <u>Section 15.2</u> (Arbitration).</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zb9ff371ab2e147a2afe67cf5a62e5f5e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">15.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="color: rgb(0, 0, 0);">The seat, or legal place, of arbitration will be New York, New York. The arbitration will be administered by the International Chamber of Commerce pursuant to its Rules of Arbitration in effect at the
                time of the arbitration, (the &#8220;</font><font style="font-weight: bold; font-style: italic; color: rgb(0, 0, 0);">Rules</font><font style="color: rgb(0, 0, 0);">&#8221;), except they may be modified as set forth herein, and applying the substantive
                law specified in <u>Section 15.5</u> (Governing Law; English Language). The language of the arbitration will be English.</font></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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">65</font></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;" noshade="noshade"></div>
    </div>
    <table id="z32ed637ba73c4a2b977e1d22305d8447" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">15.2.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="color: rgb(0, 0, 0);">Unless a Party elects for application of the ICC&#8217;s Expedited Procedure Rules pursuant to <u>Section 15.2.4</u> (Arbitration) or the Expedited Procedure Rules otherwise apply because of the amount in
                dispute, the arbitration will be conducted by a tribunal of three arbitrators. The claimant will nominate an arbitrator in its request for arbitration; the respondent will nominate an arbitrator within </font>[***] <font style="color: rgb(0, 0, 0);">of receipt of the request for arbitration; and the two-party nominated arbitrators will nominate the third, who will serve as chair of the tribunal, within </font>[***] <font style="color: rgb(0, 0, 0);">of the second
                arbitrator&#8217;s appointment. If any of the three arbitrators are not nominated within the time prescribed above, then the ICC will appoint the arbitrator(s). Within </font>[***] <font style="color: rgb(0, 0, 0);">of the commencement of
                arbitration, the Parties will attempt in good faith to reach agreement upon and thereafter follow procedures directed at assuring that the arbitration will be concluded and the award rendered within no more than </font>[***] <font style="color: rgb(0, 0, 0);">from the date the ICC Secretariat transmits the file to the arbitral tribunal. Failing such agreement, the arbitral tribunal will design and the Parties will follow procedures directed at meeting such a time
                schedule. Each arbitrator must have at least </font>[***] <font style="color: rgb(0, 0, 0);">of business or legal experience in the pharmaceutical industry. An arbitrator will be deemed to meet these qualifications unless a Party objects
                within </font>[***] <font style="color: rgb(0, 0, 0);">after the arbitrator is nominated.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5d14f19b522848b3a31da608547d31ed" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">15.2.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="color: rgb(0, 0, 0);">Notwithstanding <u>Section 15.2.3</u> (Arbitration), if the Disputed Matter involves the dispute of a Breach Notification for any default other than a determination of an alleged failure to use
                Commercially Reasonable Efforts to Develop or Commercialize the Licensed Product, the non-breaching Party may elect on notice to the breaching Party to apply the ICC Expedited Procedure Rules to the arbitration and, if such election is
                made, the number of arbitrators will be one and the period for the rendering of the final award will be </font>[***] <font style="color: rgb(0, 0, 0);">from the date of the case management conference.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z119f7ee65d25454f855fcaf0faf72669" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">15.2.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="color: rgb(0, 0, 0);">The Parties agree that any dispute concerning the propriety of the commencement of the arbitration or the scope and applicability of the agreement to arbitrate will be determined by the arbitrator(s).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zfe488fcfd50e497389441f3dd7d48fb4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">15.2.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="color: rgb(0, 0, 0);">No tribunal of arbitrators will have the power to award damages excluded pursuant to <u>Section 11.6</u> (Limitation of Liability).</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc053865c86ef41b6b0d8f3074dc8fd3e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">15.2.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="color: rgb(0, 0, 0);">Article 38 of the Rules will apply with respect to the costs of the arbitration.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z91f59e4614a64eea913fb83b865ba395" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 39.6pt; vertical-align: top;">15.2.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="color: rgb(0, 0, 0);">Except as may be required by Applicable Law, neither a Party nor any arbitrator may disclose the existence, content or results of any arbitration hereunder without the prior written consent of both Parties,
              unless to protect or pursue a legal right. The arbitral award will be final and binding on the Parties and the Parties will carry out the award without delay. Judgment on the award so rendered may be entered in any court of competent
              jurisdiction. No award or procedural order made in the arbitration shall be published.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z2bd1756775504522bbcf99d61f21a383" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Intellectual Property Disputes</font>. Notwithstanding any provision to the contrary set forth in this Agreement, if a dispute arises under this Agreement with respect to the validity, scope,
              enforceability, or ownership of any Patent Right or other intellectual property rights, and such dispute is not resolved in accordance with <u>Section 15.1</u> (Executive Officers; Disputes), then such dispute will be submitted to a court of
              competent jurisdiction in the jurisdiction in which such Patent Right or other intellectual property right was granted or arose.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">66</font></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;" noshade="noshade"></div>
    </div>
    <table id="z98eb2e01f315487b8b8333371b53cfbb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Equitable Remedies</font>. Notwithstanding any provision 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 such that a breach of <u>Article 12</u> (Confidentiality) by a Party will cause irrevocable harm for which monetary damages would not provide a sufficient remedy; and (b) in such case of such breach of <u>Article
                12</u> (Confidentiality), the non-breaching Party will be entitled to seek equitable relief, including specific performance, temporary or permanent restraining orders, preliminary injunction, permanent injunction, or other equitable relief
              without the posting of any bond or other security. In addition, and notwithstanding any provision to the contrary set forth in this Agreement, in the event of any other actual or threatened breach hereunder, the aggrieved Party may seek
              interim equitable relief (including temporary restraining orders, or other provisional equitable relief) from any court of competent jurisdiction without first submitting to the dispute resolution procedures set forth in <u>Article 15</u>
              (Dispute Resolution; Governing Law) and shall retain that right after the appointment of the arbitrator(s).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z9f96c198c6de404684ffd6788f99e000" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Governing Law; English Language</font>. This Agreement and all amendments, modifications, alterations, or supplements hereto, and the rights of the Parties, will be construed under and governed by the laws
              of the State of New York, United States, exclusive of its conflicts of laws principles. This Agreement has been prepared in the English language and the English language will control its interpretation. All consents, notices, reports, and
              other written documents to be delivered or provided by a Party under this Agreement will be in the English language, and in the event of any conflict between the provisions of any document and the English language translation thereof, the
              terms of the English language translation will control.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 16</div>
    <div style="text-align: center; font-weight: bold;">MISCELLANEOUS</div>
    <div>&#160;</div>
    <table id="z0adbec17a7624248b90e6a754e76bb91" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Assignment</font>. This Agreement may not be assigned or otherwise transferred, nor may any right or obligation hereunder be assigned or transferred, by either Party without the prior written consent of the
              other Party. Notwithstanding the foregoing, (a) Ionis may assign its rights to receive payments under this Agreement to one or more Persons (including as part of a royalty monetization transaction) (a &#8220;<font style="font-weight: bold; font-style: italic;">Payment Assignment</font>&#8221;) without consent of Otsuka; <font style="font-style: italic;">provided</font> that Ionis shall give prompt written notice to Otsuka upon making a Payment Assignment, and any assignee of a
              Payment Assignment shall not have any rights, including any audit rights, hereunder (other than the right to receive payments under this Agreement) unless Otsuka provides express prior written consent, which Otsuka may grant or withhold in
              its discretion,<font style="font-weight: bold; font-style: italic;">&#160;</font>and (b) either Party may, without consent of the other Party, assign this Agreement and its rights and obligations hereunder (i) in whole or in part to an Affiliate
              of such Party (for so long as such Affiliate remains an Affiliate), or (ii) in whole to its successor-in-interest in connection with the sale of all or substantially all of its assets, whether in a merger, acquisition, or similar transaction
              or series of related transactions. If there is an assignment pursuant to the foregoing clauses (b)(i) or (b)(ii), then such assignment will only be effective if the Person to whom this Agreement is assigned agrees in writing to assume all of
              the assigning Party&#8217;s obligations under this Agreement and the assigning Party provides written notice of such assignment to the non-assigning Party within [***] after the effective date of such assignment. Any attempted assignment of this
              Agreement in violation of this <u>Section 16.1</u> (Assignment) will be null, void, and of no legal effect. Any permitted assignee will assume all assigned obligations of its assignor under this Agreement. This Agreement will be binding on
              and will inure to the benefit of the permitted successors and assigns of the Parties.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z3963e166a6e54385b456bb268a63376c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Entire Agreement; Amendment</font>. This Agreement and the Ancillary Agreements, together with all exhibits and schedules attached hereto, constitutes the entire agreement between the Parties with respect
              to the subject matter hereof, and supersedes and merges all prior and contemporaneous negotiations, representations, and understandings regarding the same, (including that certain mutual confidential disclosure agreement between the Parties
              dated [***] (&#8220;<font style="font-weight: bold; font-style: italic;">Confidential Disclosure Agreement</font>&#8221;)). All information shared by the Parties pursuant to the Confidential Disclosure Agreement will be Confidential Information under
              this Agreement from and after the Effective Date, and the use and disclosure thereof will be governed by <u>Article 12</u> (Confidentiality). This Agreement may not be modified or amended, except by another agreement in writing executed by
              duly authorized signatories of each Party.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">67</font></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;" noshade="noshade"></div>
    </div>
    <table id="z6a285e6147a045b6a9568088c80a75db" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Strict Construction; Interpretation</font>. This Agreement has been prepared jointly and will not be strictly construed against either Party. Ambiguities, if any, in this Agreement will not be construed
              against any Party, irrespective of which Party may be deemed to have authored the ambiguous provision. Except where the context expressly requires otherwise, (a) whenever any provision of this Agreement uses the term &#8220;including&#8221; (or
              &#8220;includes&#8221;), such term will be deemed to mean &#8220;including without limitation&#8221; and &#8220;including but not limited to&#8221; (or &#8220;includes without limitations&#8221; and &#8220;includes but is not limited to&#8221;) regardless of whether the words &#8220;without limitation&#8221; or
              &#8220;but not limited to&#8221; actually follow the term &#8220;including&#8221; (or &#8220;includes&#8221;); (b) &#8220;herein,&#8221; &#8220;hereby,&#8221; &#8220;hereunder,&#8221; &#8220;hereof,&#8221; and other equivalent words will refer to this Agreement in its entirety and not solely to the particular portion of this
              Agreement in which any such word is used; (c) all definitions set forth herein will be deemed applicable whether the words defined are used herein in the singular or the plural; (d) wherever used herein, any pronoun or pronouns will be deemed
              to include both the singular and plural and to cover all genders; (e)&#160; the schedules and exhibits to this Agreement, and the terms and conditions incorporated in such schedules and exhibits will be deemed integral parts of this Agreement and
              all references in this Agreement to this Agreement will encompass such schedules and exhibits and the terms and conditions incorporated in such schedules and exhibits; <font style="font-style: italic;">provided</font> that if there is a
              conflict between the terms and conditions of this Agreement and any terms and conditions set forth in the schedules, or exhibits, then the terms of this Agreement will control; (f) in the event of any conflict between the terms and conditions
              of this Agreement and any terms and conditions that may be set forth on any order, invoice, or verbal agreement by the Parties pursuant to this Agreement, the terms and conditions of this Agreement will govern; (g) unless otherwise provided,
              all references to Sections, Articles, and Schedules in this Agreement are to Sections, Articles, and Schedules of and to this Agreement; (h) any reference to any federal, national, state, local, or foreign statute or law will be deemed to
              also refer to all rules and regulations promulgated thereunder, and any reference to any law, rule, or regulation will be deemed to include the then&#8209;current amendments thereto or any replacement or successor law, rule, or regulation thereof;
              (i) wherever used, the word &#8220;shall&#8221; and the word &#8220;will&#8221; are each understood to be imperative or mandatory in nature and are interchangeable with one another; (j) the term &#8220;or&#8221; will be interpreted in the inclusive sense commonly associated
              with the term &#8220;and/or&#8221;; (k) references to a particular Person include such Person&#8217;s successors and assigns to the extent not prohibited by this Agreement; (l) the section headings and captions used herein are inserted for convenience of
              reference only and will not be construed to create obligations, benefits, or limitations; (m) any definition of or reference to any agreement, instrument, or other document herein will be construed as referring to such agreement, instrument,
              or other document as from time to time amended, supplemented, or otherwise modified (subject to any restrictions on such amendments, supplements, or modifications set forth herein); (n) the word &#8220;notice&#8221; means notice in writing (whether or
              not specifically stated) and will include notices, consents, approvals, and other written communications contemplated under this Agreement; and (o) provisions that require that a Party, the Parties, or any committee hereunder &#8220;agree,&#8221;
              &#8220;consent,&#8221; or &#8220;approve&#8221; or the like will require that such agreement, consent, or approval be specific and in writing, whether by written agreement, letter, approved minutes, or otherwise (but excluding email and instant messaging).</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">68</font></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;" noshade="noshade"></div>
    </div>
    <table id="z3f69b75cccbf423399f2ff74a4cac0b5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Severability</font>. If any provision of this Agreement is declared invalid by a court of last resort or by any court or other governmental body the decision of which an appeal is not taken within the time
              provided by law, then and in such event, this Agreement will be deemed to have been terminated only as to the portion thereof that relates to the provision invalidated by that decision and only in the relevant jurisdiction, but this Agreement
              will remain in force, in all other respects and all other jurisdictions; <font style="font-style: italic;">provided, however</font>, that if the provision so invalidated is essential to this Agreement as a whole, then the Parties will
              negotiate in good faith to amend the terms hereof as nearly as practical to carry out the original intent of the Parties, and, failing such amendment, either Party may submit the matter for resolution pursuant to <u>Article 15</u><font style="color: rgb(0, 0, 0);">&#160;</font>(Dispute Resolution; Governing Law).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd9ed65b937084fcd84ceb94f020eb94a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><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 of this Agreement when such failure or delay is due to Force Majeure. For purposes of this Agreement, &#8220;<font style="font-weight: bold; font-style: italic;">Force Majeure</font>&#8221; is defined as any cause
              beyond the 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. Notwithstanding the foregoing, a Party will not be excused from making payments owed hereunder due
              to any such Force Majeure circumstances affecting such Party. The Party affected by 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 [***], 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 this Agreement. To the extent possible, each Party will use reasonable efforts to minimize the duration of any Force Majeure.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z0a661d20ef7e4fcd843338a66da06211" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Notices</font>. All notices that are required or permitted hereunder will be in writing and sufficient if delivered by internationally-recognized overnight courier or sent by registered or certified mail,
              postage prepaid, return receipt requested, and in each case, addressed as follows (with a courtesy copy sent by email, which will not constitute notice):</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 50.4pt;">If to Ionis:</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt;">Ionis Pharmaceuticals, Inc.</div>
    <div style="margin-left: 72pt;">2855 Gazelle Court </div>
    <div style="margin-left: 72pt;">Carlsbad, CA 92010</div>
    <div style="margin-left: 72pt;">Attention: Chief Business Officer</div>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 50.4pt;"><font style="font-style: italic;">With a copy (which will not constitute notice </font>for purposes of this Agr<font style="font-style: italic;">eement) to each of</font>:</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt;">[***]</div>
    <div style="margin-left: 72pt;">Attention: General Counsel</div>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 50.4pt;">If to Otsuka:</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt;">Otsuka Pharmaceutical Co., Ltd.</div>
    <div style="margin-left: 72pt;">Shinagawa Grand Central Tower</div>
    <div style="margin-left: 72pt;">2-16-4 Konan, Minato-ku</div>
    <div style="margin-left: 72pt;">Tokyo, 108-8242 Japan</div>
    <div style="margin-left: 72pt;">Attn:&#160; Director, Global Business Development</div>
    <div style="margin-left: 72pt;">Email:&#160; [***]</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">69</font></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;" noshade="noshade"></div>
    </div>
    <div style="text-align: justify; margin-left: 50.4pt;"><font style="font-style: italic;">With a copy (which will not constitute notice for purposes of this Agreement) to</font>:</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt;">Otsuka Pharmaceutical Co., Ltd.</div>
    <div style="margin-left: 72pt;">Shinagawa Grand Central Tower</div>
    <div style="margin-left: 72pt;">2-16-4 Konan, Minato-ku</div>
    <div style="margin-left: 72pt;">Tokyo, 108-8242 Japan</div>
    <div style="margin-left: 72pt;">Attn:&#160; Director, Legal Affairs Department</div>
    <div style="margin-left: 72pt;">Email:&#160; [***]</div>
    <div><br>
    </div>
    <div style="margin-left: 72pt;">Otsuka Pharmaceutical Europe Ltd.</div>
    <div style="margin-left: 72pt;">2 Windsor Dials, Arthur Road,</div>
    <div style="margin-left: 72pt;">Windsor, SL4 1RS, United Kingdom</div>
    <div style="margin-left: 72pt;">Attn: General Counsel</div>
    <div style="margin-left: 72pt;">Email: [***]</div>
    <div><br>
    </div>
    <div style="text-align: justify; margin-left: 72pt;">or to such other address as the Party to whom notice is to be given may have furnished to the other Party in writing in accordance herewith. Any such notice will be deemed to have been given: (a) on
      the Business Day after dispatch if sent by internationally-recognized overnight courier; or (b) on the fifth Business Day after dispatch if sent by registered or certified mail, postage prepaid, return receipt requested.</div>
    <div>&#160;</div>
    <table id="za40c73f51fdb41e2954443133a34ae30" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Further Assurances</font>. The Parties agree to reasonably cooperate with each other in connection with any actions required to be taken as part of their respective obligations under this Agreement, and
              will (a) furnish to each other such further information; (b) execute and deliver to each other such other documents; and (c) do such other acts and things (including working collaboratively to correct any clerical, typographical, or other
              similar errors in this Agreement), all as the other Party may reasonably request for the purpose of carrying out the intent of this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z6bd8aa5627954f07b71e57039a166830" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Performance by Affiliates</font>. Notwithstanding any provision to the contrary set forth in this Agreement, either Party will have the right to perform any or all of its obligations and exercise any or all
              of its rights under this Agreement through any Affiliate. 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.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="ze137eba0f2624fbfb0433941908390a7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Agency</font>. Neither Party is, nor will be deemed to be an employee, agent, or representative of the other Party for any purpose. Each Party is an independent contractor, not an employee or partner of the
              other Party. Neither Party will have the authority to speak for, represent, or obligate the other Party in any way without prior written authority from the other Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z3fcbfec2d43848f49b39b0a966a8dbd0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Binding Effect; No Third-Party Beneficiaries or Obligors</font>. As of the Effective Date, this Agreement will be binding upon and inure to the benefit of the Parties and their respective permitted
              successors and assigns. Except as set forth in <u>Article 13</u> (Indemnification), no Person other than Ionis, Otsuka, and their respective permitted successors and assigns hereunder will be deemed an intended beneficiary hereunder, nor
              have any right to enforce any obligation of any Party to this Agreement, nor will any Person other than Ionis and Otsuka and their respective permitted successors and assigns have any obligations to any Party under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.11</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Waiver</font>. Any omission or delay by either Party at any time to enforce any right or remedy reserved to it, or to require performance of any of the terms, covenants, or provisions hereof, by the
              other Party, will not constitute a waiver of such Party&#8217;s rights to the future enforcement of its rights under this Agreement. Any waiver by a Party of a particular breach or default by the other Party will not operate or be construed as a
              waiver of any subsequent breach or default by the other Party.</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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">70</font></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;" noshade="noshade"></div>
    </div>
    <table id="zb59c9074c1ab4c5596823b0d6bed6c05" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.12</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cumulative Remedies</font>. No remedy referred to in this Agreement, including termination of this Agreement, is intended to be exclusive, but each will be cumulative and in addition to any other remedy
              referred to in this Agreement or otherwise available under law.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z2d7e6a78267d4f9ab28fda5589be022f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.13</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Counterparts</font>. This Agreement may be executed in one or more counterparts, all of which taken together will be regarded as one and the same instrument. Each Party may execute this Agreement in Adobe&#8482;
              Portable Document Format (PDF) sent by electronic mail. PDF signatures of authorized signatories of the Parties 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>
    <div style="text-align: center; font-style: italic;">[Remainder of page intentionally left blank; Signature page follows.]</div>
    <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; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">71</font></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;" noshade="noshade"></div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">IN WITNESS WHEREOF,</font> the Parties have executed this Agreement through their duly authorized representatives to be effective as of the Effective Date.</div>
    <div>&#160;</div>
    <table id="z28baced148ce49c2a4d5649cc0cd5767" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
          </td>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; color: rgb(0, 0, 0); font-weight: bold;">Otsuka Pharmaceutical Co., Ltd.</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3" rowspan="1">&#160;</td>
          <td style="vertical-align: top;" colspan="3" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 3%; vertical-align: top; padding-bottom: 2px;">
            <div style="text-align: justify; color: rgb(0, 0, 0);">By:&#160;&#160;</div>
          </td>
          <td style="width: 42%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); text-indent: 18pt;"><font style="font-style: italic;">/s/ Brett Monia, PhD</font></td>
          <td style="width: 5%; vertical-align: top; padding-bottom: 2px;"><br>
          </td>
          <td style="width: 3%; vertical-align: top; padding-bottom: 2px;">
            <div style="text-align: justify; color: rgb(0, 0, 0);">By:&#160;&#160;</div>
          </td>
          <td style="width: 42%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); text-indent: 18pt;"><font style="font-style: italic;">/s/ Makoto Inoue</font></td>
          <td style="width: 5%; vertical-align: top; padding-bottom: 2px;"><br>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; color: rgb(0, 0, 0);">Name:&#160; Brett Monia, PhD</div>
          </td>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; color: rgb(0, 0, 0);">Name: Makoto Inoue</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; color: rgb(0, 0, 0);">Title:&#160; Chief Executive Officer</div>
          </td>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; color: rgb(0, 0, 0);">Title:&#160; President and Representative Director</div>
          </td>
        </tr>

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

        <tr>
          <td style="width: 50%; vertical-align: top;"><br>
          </td>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; color: rgb(0, 0, 0); font-weight: bold;">Otsuka Pharmaceutical Co., Ltd.</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="vertical-align: top;" rowspan="1" colspan="3">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
          <td style="width: 3%; vertical-align: top; padding-bottom: 2px;">
            <div style="text-align: justify; color: rgb(0, 0, 0);">By:&#160;&#160;<font style="font-style: italic;"></font></div>
          </td>
          <td style="width: 42%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); text-indent: 18pt;"><font style="font-style: italic;">/s/ Takeshi Watanabe</font></td>
          <td style="width: 5%; vertical-align: top; padding-bottom: 2px;"><br>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; color: rgb(0, 0, 0);">Name:&#160; Takeshi Watanabe, PhD, MBA</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; color: rgb(0, 0, 0);">Title:&#160; VP, Global Head of Business Development</div>
          </td>
        </tr>

    </table>
    <div> <br>
    </div>
    <div>
      <div style="text-align: center;">[Signature Page to License Agreement]</div>
      <div> <br>
      </div>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <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;" noshade="noshade"></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>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">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 id="zc2f83999cb9b42dfb0352d4a1ef53c73" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Accounting Standards</font>&#8221; means, with respect to a Party or its Affiliate or Sublicensee, GAAP or IFRS, as such Person uses for its financial reporting standards from time to time,
              in each case, as consistently applied.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zbe6890fe56f44ce694ff1a2f4c6120e0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Affiliate</font>&#8221; means, with respect to a Person, any corporation or other business entity controlled by, controlling, or under common control with such Person, with &#8220;control&#8221; meaning
              (a) direct or indirect beneficial ownership of more than 50% of the voting stock or other ownership interest of, or more than 50% interest in the income of, the applicable entity, or (b) the possession, directly or indirectly, of the power to
              direct the management or policies of the applicable entity, whether through the ownership of voting securities or other equity rights, by contract relating to voting rights or corporate governance, or otherwise. Notwithstanding the foregoing,
              for purposes of this Agreement, &#8220;Affiliates&#8221; will not include, (a) with respect to an entity, <font style="font-style: italic;">bona fide</font> venture capital investors in such entity or <font style="font-style: italic;">bona fide</font>
              institutional investors in such entity, in each case, that routinely make venture capital investments for the potential financial return on such investments and not with any view to acquisition or for other strategic purpose, or Affiliates of
              such venture capital or institutional investors, or (b) with respect to Otsuka, any entities that are controlled by Otsuka Holdings Co., Ltd. but are not subsidiaries of Otsuka.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z07074c30886c4825a3286313e54098bd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Alliance Manager</font>&#8221; has the meaning set forth in <u>Section 8.7</u> (Alliance Managers).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z8f3ad7f3823947cca8a6c54a6fa30bb3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; means any [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd18aafac7c414f0f9677527cb3d0cab1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ancillary Agreements</font>&#8221; means the Pharmacovigilance Agreement, each Supply Agreement, and each Quality Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7f3774ae2dc5464d83ab69c2b63d231e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">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 id="z7cac0a209a5a424fb8595007dd6dd251" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Approved Labeling</font>&#8221; means, with respect to a Licensed Product and a jurisdiction: (a) the applicable Regulatory Authority-approved full prescribing information for such Licensed
              Product in such jurisdiction; and (b) the applicable Regulatory Authority-approved labels and any other written, printed, or graphic materials on any container, wrapper, or any package insert that is used with or for such Licensed Product in
              such jurisdiction.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="za1691230a00443f888a640a463acba0e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">ASMF</font>&#8221; has the meaning set forth in <u>Section 5.3</u> (Correspondences with Regulatory Authorities).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zff25b0441dfd4b5fb4dfab6c089a7a38" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Blocking Identified Rights</font>&#8221; has the meaning set forth in <u>Section 2.7.2(a)ii</u> (Acquisition of Potential In-Licenses).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z8bc411948b8c41bfbee1b1a0ad20ed2b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Breach Notification</font>&#8221; has the meaning set forth in <u>Section 14.2.1</u> (Material Breach).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <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;" noshade="noshade"></div>
    </div>
    <table id="z5abdf931efef47a5888d8311ba0f4eea" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.11</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Business Day</font>&#8221; means a day other than (a) a Saturday, Sunday, (b) a day on which banking institutions in California, Tokyo, Japan, or London, England are required by Applicable
              Law to remain closed or (c) the nine consecutive days beginning on December 24 and continuing through January 1, to the extent not already covered in clause (a) or clause (b).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd0ebe3da8539475782157f28ba8bb835" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.12</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Calendar Quarter</font>&#8221; means, with respect to the first Calendar Quarter during the Term, the period beginning on the Effective Date and ending on the last day of the Calendar Quarter
              within which the Effective Date falls, and thereafter each successive period of three calendar months ending on (and including) each of March 31, June 30, September 30, and December 31; except that the last Calendar Quarter during the Term
              will end upon the expiration of the Term.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="ze93e6223b77b44859161c39391a160dc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.13</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Calendar Year</font>&#8221; means the period of 12 consecutive calendar months beginning on January 1 and ending on December 31; except that (a) the first Calendar Year during the Term will
              begin on the Effective Date and end on December 31 of the Calendar Year within which the Effective Date falls, and (b) the last Calendar Year during the Term will end upon expiration of the Term.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5ed24575525346e1bf50a7c42df9f163" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.14</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Change of Control</font>&#8221; means, with respect to a Party, that: (a) any Third Party acquires directly or indirectly the beneficial ownership of any voting security of such Party, or if
              the percentage ownership of such Third Party in the voting securities of such Party is increased through stock redemption, cancellation, or other recapitalization, and immediately after such acquisition or increase such Third Party is,
              directly or indirectly, the beneficial owner of voting securities representing more than 50% of the total voting power of all of the then outstanding voting securities of such Party; (b) a merger, consolidation, recapitalization, or
              reorganization of such Party is consummated that would result in shareholders or equity holders of such Party immediately prior to such transaction owning 50% or less of the outstanding voting securities of the surviving entity (or its parent
              entity) immediately following such transaction; or (c) the sale or transfer to a Third Party, in one or more related transactions, of all or substantially all of such Party&#8217;s consolidated assets taken as a whole.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zf2f344544b88447295c1f8ce05eda747" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.15</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Clinical Supply Agreement</font>&#8221; has the meaning set forth in <u>Section 7.2.1</u> (Clinical Supply Agreement).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z65cccd0b1e9c45cc86081f9890e1dbd8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.16</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Clinical Trial</font>&#8221; means any clinical trial in humans.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z1d6053b3595b470194df9d13c1f67a23" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.17</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">CMC</font>&#8221; means chemistry, manufacturing, and controls.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z1e6747bc9e5843a780981b8af0fee1ad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.18</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">CMO</font>&#8221; has the meaning set forth in <u>Section 7.3.1</u> (By Otsuka).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zec9c7fa8230741ef9f30abdfd67f9d78" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.19</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Collaboration In-License</font>&#8221; means (a) any Potential In-License that [***] in accordance with <u>Section 2.7.2(b)</u> (Collaboration In-Licenses) and (b) any Existing Third-Party
              IP Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z28ba94b3ceb44bb29d5d10b81139929e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.20</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Collaboration Know-How</font>&#8221; means all Know-How developed or invented by a Party&#8217;s or its Affiliates&#8217;, licensees&#8217;, Sublicensees&#8217;, or Subcontractors&#8217; employees, agents, or independent
              contractors, or any Persons contractually required to assign or license such Know-How to such Party or any Affiliate of such Party, either alone or jointly with the other Party&#8217;s or its Affiliates&#8217;, licensees&#8217;, Sublicensees&#8217;, or
              Subcontractors&#8217; employees, agents, or independent contractors, or any Persons contractually required to assign or license such Know-How to such other Party or any Affiliate of such other Party, in each case, in the performance of activities
              under this Agreement during the Term.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.21</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Collaboration Patent Rights</font>&#8221; means any Patent Right that (a) has a priority date after the Effective Date and (b) Covers any Invention included in the Collaboration Know-How.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.22</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Combination Product</font>&#8221; has the meaning set forth in <u>Section 1.136</u> of this <u>Appendix 1</u> (Definitions).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.23</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Combination Product Net Sales</font>&#8221; has the meaning set forth in <u>Section 1.136</u> of this <u>Appendix 1</u> (Definitions).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.24</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Commercial Supply Agreement</font>&#8221; has the meaning set forth in <u>Section 7.2.2</u> (Commercial Supply Agreement).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.25</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Commercialization</font>&#8221; means any and all activities directed to the marketing, promotion, distribution, pricing, reimbursement, offering for sale, and sale of a pharmaceutical or
              biologic product and interacting with Regulatory Authorities following receipt of Regulatory Approval in the applicable country or region for such pharmaceutical or biologic product regarding the foregoing, including seeking and maintaining
              any required Reimbursement Approval, but excluding activities directed to Manufacturing or Development. &#8220;<font style="font-weight: bold; font-style: italic;">Commercialize</font>,&#8221; &#8220;<font style="font-weight: bold; font-style: italic;">Commercializing</font>,&#8221;
              and &#8220;<font style="font-weight: bold; font-style: italic;">Commercialized</font>&#8221; will be construed accordingly.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.26</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Commercially Reasonable Efforts</font>&#8221; means, with respect to the Exploitation of a Licensed Product by a Party, [***].</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.27</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Competitive Infringement</font>&#8221; means any infringement, unauthorized use, misappropriation or threatened infringement or misappropriation by a Third Party with respect to any Ionis
              Technology, Otsuka Technology, or Joint Collaboration Technology by reason of the making, using, offering to sell, selling or importing of a compound, product, method, or process that would be competitive with a Licensed Product then being
              Developed or Commercialized in the Field.</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.28</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Confidential Disclosure Agreement</font>&#8221; has the meaning set forth in <u>Section 16.2</u> (Entire Agreement; Amendment).</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.29</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Confidential Information</font>&#8221; means, subject to <u>Section 12.3</u> (Exemptions), (a) Know-How and any technical, scientific, trade, research, Manufacturing, business, financial,
              marketing, product, supplier, intellectual property, and other non-public or proprietary data or information (including unpublished patent applications) that may be disclosed by one Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Disclosing Party</font>&#8221;) or its Affiliates to the other Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Receiving Party</font>&#8221;) or its Affiliates pursuant to this Agreement (including information disclosed prior
              to the Effective Date pursuant to the Confidential Disclosure Agreement), regardless of whether such information is specifically marked or designated as confidential and regardless of whether such information is in written, oral, electronic,
              or other form, and (b) the terms of this Agreement.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.30</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Continuing Know-How Transfer</font>&#8221; has the meaning set forth in <u>Section 3.1</u> (Initial Know-How Transfer).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.31</td>
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            <div><font style="font-weight: bold;">&#8220;</font><font style="font-weight: bold; font-style: italic;">Control</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">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, licenses, or sublicense or incurring any additional payment obligations to a Third Party that would not be incurred but for such access, right to use, licenses, or sublicense,
              other than payment obligations incurred under a Collaboration In-License, and (c) with respect to any product, the possession by a Party of the ability (whether by sole or joint ownership, license, or otherwise, other than pursuant to the
              licenses granted under this Agreement) to grant an exclusive license or sublicense of Patent Rights that Cover such product or proprietary Know-How that is used in connection with the Exploitation of such product. Notwithstanding the
              foregoing, [***].</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.32</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Core or Manufacturing Identified Rights</font>&#8221; has the meaning set forth in <u>Section 2.7.2(a)i</u> (Acquisition of Potential In-Licenses).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.33</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Core or Manufacturing Potential In-License</font>&#8221; has the meaning set forth in <u>Section 2.7.2(a)i </u>(Acquisition of Potential In-Licenses).</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.34</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Cost Overrun</font>&#8221; has the meaning set forth in <u>Section 4.4.2(b)</u> (Cost Overruns).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.35</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Cover</font>&#8221; means, with respect to a particular subject matter at issue and a relevant Patent Right or individual claim in such Patent Right, as applicable, that the manufacture, use,
              sale, offer for sale, or importation of such subject matter would fall within the scope of one or more claims in such Patent Right.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.36</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Cross-Territory Clinical Development Plan</font>&#8221; has the meaning set forth in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan).</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.37</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Cross-Territory Clinical Studies</font>&#8221; has the meaning set forth in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.38</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Debarred/Excluded</font>&#8221; has the meaning set forth in <u>Section 11.1.5</u> (Mutual Representations and Warranties).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.39</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Development</font>&#8221; means all internal and external research, development and regulatory activities regarding pharmaceutical or biologic products, 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 a pharmaceutical or biologic product, but excluding activities directed to Manufacturing or Commercialization. Development
              will include development and regulatory activities for additional presentations or indications for a product after receipt of Regulatory Approval of such product, including Post-Approval Mandatory Studies. &#8220;<font style="font-weight: bold; font-style: italic;">Develop</font>,&#8221; &#8220;<font style="font-weight: bold; font-style: italic;">Developing</font>,&#8221; and &#8220;<font style="font-weight: bold; font-style: italic;">Developed</font>&#8221; will be construed accordingly.</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.40</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Development Cost Share Notice</font>&#8221; has the meaning set forth in <u>Section 4.4.3</u> (Shared Cross-Territory Development Costs).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.41</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Disclosing Party</font>&#8221; has the meaning set forth in <u>Section 1.29</u> (Confidential Information) of this <u>Appendix 1</u> (Definitions).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.42</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Disputed Matter</font>&#8221; has the meaning set forth in <u>Section 15.1</u> (Executive Officers: Disputes).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.43</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Effective Date</font>&#8221; has the meaning set forth in the Preamble.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.44</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Eligible Cross-Territory Development Costs</font>&#8221; has the meaning set forth in <u>Section 4.4.3</u> (Shared Cross-Territory Development Costs).</div>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.45</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">EMA</font>&#8221; means the European Medicines Agency or any successor agency thereto.</div>
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        </tr>

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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.46</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">European Union</font>&#8221; or &#8220;<font style="font-weight: bold;">E.U.</font>&#8221; means the economic, scientific, and political organization of member states of the European Union as it may be
              constituted from time to time.</div>
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    </table>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.47</td>
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            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 7.2.6</u> ([***]).</div>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.48</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Executive Officer</font>&#8221; means (a) with respect to Otsuka, its President and Representative Director or their designee and (b) with respect to Ionis, the Chief Executive Officer or
              their designee.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.49</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Existing Third-Party IP Agreement</font>&#8221; means any agreement between Ionis (or any of its Affiliates) and any Third Party entered into prior to the Effective Date under which Ionis (or
              any of its Affiliates) obtained a license or other right to any of such Third Party&#8217;s Know-How or Patent Rights that fall within the definition of any of the Ionis Technology.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.50</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Exploit</font>&#8221; means to make, have made, use, offer to sell, sell, Develop, Manufacture, Commercialize, or otherwise exploit. &#8220;<font style="font-weight: bold; font-style: italic;">Exploitation</font>&#8221;
              will be construed accordingly.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.51</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">External Costs</font>&#8221; mean, with respect to a Party, the documented actual expenses paid to Third Parties (or payable to Third Parties and accrued in accordance with such Party&#8217;s
              Accounting Standards) by such Party (or its Affiliate) in consideration of the performance of activities under this Agreement, without mark-up, and excluding any costs or expenses included under the FTE Rate.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.52</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">FD&amp;C Act</font>&#8221; means the United States Federal Food, Drug and Cosmetic Act, as amended from time-to-time, together with any rules, regulations, and requirements promulgated
              thereunder (including all additions, supplements, extensions, and modifications thereto).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.53</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">FDA</font>&#8221; means the U.S. Food and Drug Administration or any successor agency thereto.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.54</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Field</font>&#8221; means for the treatment or prevention of any diseases and conditions in humans.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.55</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Filing Party</font>&#8221; has the meaning set forth in <u>Section 5.5</u> (Regulatory Submissions).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.56</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">First Commercial Sale</font>&#8221; means, with respect to a Licensed Product in a country, the first sale for end use or consumption to a Third Party of such Licensed Product in such country
              by a Party, or its Affiliates or Sublicensees after the receipt of Regulatory Approval and Reimbursement Approval in the Field for such Licensed Product by the relevant Regulatory Authority in such country. First Commercial Sale excludes any
              sale or other distribution for use in a Clinical Trial or other Development activity or for compassionate use,&#160;named-patient use, or expanded access, indigent or other patient access programs when sold or distributed at or below the
              applicable Selling Party&#8217;s costs.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.57</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 9.3.4(a)</u> ([***]).</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.58</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Product</font>&#8221; has the meaning set forth in <u>Section 2.8.1</u> (ROFN Exercise).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.59</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Product Activities</font>&#8221; has the meaning set forth in <u>Section 2.8.3</u> (Follow-On Product Activities).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc48e5ec6cceb4198a230e608a37942db" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.60</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Force Majeure</font>&#8221; has the meaning set forth in <u>Section 16.5</u> (Force Majeure).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.61</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">FTE</font>&#8221; means the equivalent of the work of one duly qualified employee of a Party full time for one year (consisting of a total of [***] hours per year) directly carrying out [***]
              activities under this Agreement. Overtime, and work on weekends, holidays and the like will not be counted with any multiplier (<font style="font-style: italic;">e.g.</font>, time-and-a-half or double time) toward the number of hours that are
              used to calculate the FTE contribution, and no individual may be charged at greater than one FTE, regardless of that individual&#8217;s hours worked during that year. The portion of an FTE billable by a Party for one employee during a given
              accounting period will be determined by dividing the number of hours worked directly by such employee on the work to be conducted under this Agreement during such accounting period by the number of FTE hours applicable for such accounting
              period based on [***] working hours per Calendar Year. For clarity, travel time spent by an employee, unless also spent working directly on activities under this Agreement, will not be included in the number of hours used to calculate the FTE
              contribution.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.62</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">FTE Rate</font>&#8221; means [***] per FTE per hour. For the avoidance of doubt, such FTE Rate will be [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.63</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Future Cross-Territory Studies</font>&#8221; has the meaning set forth in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.64</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">GAAP</font>&#8221; means the generally accepted accounting principles in the United States.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.65</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Generic Product</font>&#8221; means, with respect to a Licensed Product in a country, a pharmaceutical product (other than such Licensed Product) that (a) is expected to be sold by a Third
              Party other than a Sublicensee under license from Otsuka in such country, (b) is authorized for use in such country in one or more of the indications for which such Licensed Product has Regulatory Approval in such country; and (c) contains
              the same active pharmaceutical ingredient(s) as such Licensed Product. A product will not be considered to be a Generic Product if (i) Otsuka or any of its Affiliates or Sublicensees was involved in or authorized the Development or
              Commercialization of such product, (ii) Otsuka or any of its Affiliates or Sublicensees has granted a license to such Third Party in respect of such product, or (iii) such product is Commercialized by any Person who obtained such product in a
              chain of distribution that included Otsuka or any of its Affiliates or Sublicensees.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.66</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Global Brand Strategic and Operating Plan</font>&#8221; has the meaning set forth in <u>Section 6.4</u> (Global Brand Strategic and Operating Plan).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.67</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Global Medical Affairs Plan</font>&#8221; has the meaning set forth in <u>Section 6.7.1</u> (Global Medical Affairs Plan).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.68</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Global Trade Control Laws</font>&#8221; means the U.S. Export Administration Regulations, the U.S. International Traffic in Arms Regulations, the economic sanctions regulations administered
              by the U.S. Treasury Department&#8217;s Office of Foreign Assets Control, E.U. Council Regulations on export controls, including Nos. 428/2009, 267/2012, other E.U. Council sanctions regulations, as implemented in the E.U. member states, United
              Nations sanctions policies, and all relevant regulations made under any of the foregoing.</div>
          </td>
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    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.69</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Good Clinical Practices</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">GCP</font>&#8221; means the then-current good clinical practice standards, practices, and procedures
              promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zf8b44145752241c386b1928842155d22" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.70</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Good Laboratory Practices</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">GLP</font>&#8221; means the then-current good laboratory practice standards, practices, and
              procedures promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z00c56a3c27614ebdb0442b588f0809d2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.71</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Good Manufacturing Practices</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">GMP</font>&#8221; means the then-current good manufacturing practice standards, practices, and
              procedures promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zffae1fda7cfa49dd8ae1ecf299654dda" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.72</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Government Official</font>&#8221; means any official, officer, employee, or representative of: (a) any federal, state, provincial, administrative division, county, or municipal government or
              any department or agency thereof; (b) any public international organization or any department or agency thereof; or (c) any company or other entity owned or controlled by any government or Governmental Authority.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.73</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Governmental Authority</font>&#8221; means any court, agency, department, authority, tribunal, or other instrumentality of any supra-national, national, state, provincial, county, city, or
              other political subdivision. For clarity, Governmental Authorities include all Regulatory Authorities.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.74</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">HAE</font>&#8221; means hereditary angioedema.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.75</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Identified Rights</font>&#8221; has the meaning set forth in <u>Section 2.7.1</u> (Identification of New In-License Agreements).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.76</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">IFRS</font>&#8221; means International Financial Reporting Standards, consistently applied.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.77</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">IND</font>&#8221; means an Investigational New Drug application required pursuant to 21 C.F.R. Part 312 or any comparable filings outside of the U.S. required to commence human clinical
              trials in such country or region (such as an application for a Clinical Trial Authorization in the E.U.), and all supplements or amendments that may be filed with respect to the foregoing.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zdebc2f501d7b4d8e84a7e040b9a3a8ce" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.78</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Indemnified Party</font>&#8221; has the meaning set forth in <u>Section 13.3</u> (Indemnification Procedure).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.79</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Indemnifying Party</font>&#8221; has the meaning set forth in <u>Section 13.3</u> (Indemnification Procedure).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.80</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Initial Know-How Transfer</font>&#8221; has the meaning set forth in <u>Section 3.1</u> (Initial Know-How Transfer).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.81</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Initial Royalties</font>&#8221; has the meaning set forth in <u>Section 9.3.1</u> (Royalty Payments During the Initial Royalty Term).</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.82</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Initial Royalty Term</font>&#8221; has the meaning set forth in <u>Section 9.3.1</u> (Royalty Payments During the Initial Royalty Term).</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.83</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Initiation</font>&#8221; means dosing of the first patient in a Clinical Trial.</div>
          </td>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.84</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Internal Costs</font>&#8221; means, for any period of time, the product obtained by multiplying (a) the total FTEs (or portion thereof) devoted to the performance of activity under this
              Agreement during such period, by (b) the applicable FTE Rate for such period; <font style="font-style: italic;">provided </font>that [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.85</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Invention</font>&#8221; means any process, method, composition of matter, article of manufacture, discovery, or finding that is conceived or reduced to practice (whether or not patentable).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zdfcb6349e3604ed0aed17a28a86fb3ff" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.86</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Attribution Language</font>&#8221; has the meaning set forth in <u>Section 12.7.2</u> (Acknowledgement).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zf89322ec6eae40f1bd16990077fce976" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.87</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Know-How</font>&#8221; has the meaning set forth in <u>Section 10.1.2(a)</u> (Ownership of Arising Intellectual Property).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.88</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Patent Rights</font>&#8221; has the meaning set forth in <u>Section 10.1.2(a)</u> (Ownership of Arising Intellectual Property).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z87f93999bd5a4fef93ebe20395411576" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.89</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Core Technology</font>&#8221; means Ionis Core Technology Know-How and the Ionis Core Technology Patents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z8246cb32733a46899463bae94ac603fc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.90</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Core Technology Know-How</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), all Know-How, including Ionis Collaboration Know-How but excluding Ionis
              Product-Specific Know-How, Ionis Manufacturing and Analytical Know-How and Ionis&#8217; interest in any Joint Collaboration Know-How, that (a) is Controlled by Ionis or its Affiliates as of the Effective Date or at any time during the Term, (b) is
              necessary or reasonably useful to Exploit a Licensed Product, and (c) relates generally to oligonucleotide.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zdfb5cdee7c7f4a20824617ee8843be91" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.91</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Core Technology Patents</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), any Patent Rights, including Ionis Collaboration Patent Rights but excluding Ionis
              Product-Specific Patents, Ionis Manufacturing and Analytical Patents and Ionis&#8217; interest in any Joint Collaboration Patent Rights, that (a) are Controlled by Ionis or its Affiliates as of the Effective Date or at any time during the Term, (b)
              are necessary or reasonably useful (or, with respect to patent applications, would be necessary or reasonably useful if such patent applications were to issue as patents) to Exploit a Licensed Product and (c) Cover subject matter generally
              applicable to oligonucleotides. <font style="color: rgb(0, 0, 0);">A list of the </font>Ionis Core Technology Patents <font style="color: rgb(0, 0, 0);">as of the </font>Effective Date <font style="color: rgb(0, 0, 0);">is set forth on </font><font style="font-variant: small-caps; color: rgb(0, 0, 0);"><u>Schedule 1.91</u></font><font style="color: rgb(0, 0, 0);"> (Ionis Core Technology Patents)</font>; <font style="font-style: italic;">provided</font> that, any Patent Right existing
              as of the Effective Date that otherwise would be included in the definition of Ionis Core Technology Patents but is not included on <font style="font-variant: small-caps; color: rgb(0, 0, 0);"><u>Schedule 1.91</u></font><font style="color: rgb(0, 0, 0);"> (Ionis Core Technology Patents) </font>will still be considered a Ionis Core Technology Patent<font style="color: rgb(0, 0, 0);">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5114009a91ae4d8cbd054c5956df5dbe" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.92</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Indemnitee</font>&#8221; has the meaning set forth in <u>Section 13.2</u> (Indemnification by Otsuka).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z79a50dc399b34f5395ade58de5f44418" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.93</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Internal Oligonucleotide Safety Database</font>&#8221; has the meaning set forth in <u>Section 5.12.1</u> (Ionis Internal Oligonucleotide Safety Database).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z609b379d20d34802b2c2c8a225f088bd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.94</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Know-How</font>&#8221; means the Ionis Core Technology Know-How, Ionis Manufacturing and Analytical Know-How, and Ionis Product-Specific Know-How.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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        <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.95</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Manufacturing and Analytical Know-How</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), Know-How, including Ionis Collaboration Know-How but excluding Ionis&#8217;
              interest in any Joint Collaboration Know-How, that (a) is Controlled by Ionis or its Affiliates as of the Effective Date or at any time during the Term, (b) is necessary or reasonably useful to Exploit a Licensed Product, and (c) relates to
              any Manufacturing Technology.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zb48b77ff76134099a22376b585fb9719" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.96</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Manufacturing and Analytical Patents</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), Patent Rights, including Ionis Collaboration Patent Rights but excluding
              Ionis&#8217; interest in any Joint Collaboration Patent Rights, that (a) are Controlled by Ionis or its Affiliates on the Effective Date or at any time during the Term, (b) are necessary or reasonably useful (or, with respect to patent
              applications, would be necessary or reasonably useful if such patent applications were to issue as patents) to Exploit a Licensed Product, and (c) Cover Manufacturing Technology. A list of Ionis Manufacturing and Analytical Patents as of the
              Effective Date is set forth on <font style="font-variant: small-caps;"><u>Schedule 1.96</u></font> (Ionis Manufacturing and Analytical Patents); <font style="font-style: italic;">provided</font> that, any Patent Right existing as of the
              Effective Date that otherwise would be included in the definition of Ionis Manufacturing and Analytical Patent but is not included on <font style="font-variant: small-caps;"><u>Schedule 1.96</u></font> (Ionis Manufacturing and Analytical
              Patents) will still be considered a Ionis Manufacturing and Analytical Patent.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5df98c4792b1465c8aa57143e6ad0f13" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.97</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Manufacturing and Analytical Technology</font>&#8221; means Ionis Manufacturing and Analytical Know-How and Ionis Manufacturing and Analytical Patents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="ze3dbcaad33b343ed8848a86ee627e1ad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.98</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis </font>[***] <font style="font-weight: bold; font-style: italic;">Costs</font>&#8221; has the meaning set forth in <u>Section 4.4.4(c)</u> (Otsuka Opt-In).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="za6dd062e658b4aa2a38e98e1181fd59a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.99</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis </font>[***]&#8221; has the meaning set forth in <u>Section 4.4.4(b)</u> ([***] by Ionis).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="za88dbbf6c1814b4caf80044200bfd7fe" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.100</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis </font>[***]&#8221; means [***] generated by or on behalf of Ionis in the [***] in accordance with <u>Section 4.4.4(b)</u> ([***] by Ionis).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7f77be45c2664c84abbccd1a53e980fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.101</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Patent Rights</font>&#8221; means the Ionis Core Technology Patents, Ionis Manufacturing and Analytical Patents, and Ionis Product-Specific Patents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7c92ef5207c34e319bba5eb08378dfd9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.102</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product-Specific Know-How</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), all Know-How, including Ionis Collaboration Know-How but excluding Ionis&#8217; interest
              in any Joint Collaboration Know-How, that is (a) Controlled by Ionis or its Affiliates as of the Effective Date or at any time during the Term, (b) necessary or reasonably useful to Exploit a Licensed Product in the Field, and (c)
              specifically relating to (i) the composition of matter of a Licensed Product or (ii) methods of using a Licensed Product for the Field; <font style="font-style: italic;">provided however</font>, Know-How that (i) consists of subject matter
              applicable to oligonucleotide compounds or products in general or (ii) relates to an oligonucleotide compound that does not specifically modulate expression of PKK via the binding, partially or wholly, of such compound to RNA that encodes
              PKK, will not be considered Ionis Product-Specific Know-How, and in each case of (i) and (ii), such Know-How will be considered Ionis Core Technology Know-How.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zb91fbf49d3934af4b225e5c545253ae7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.103</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product-Specific Patents</font>&#8221; means, subject to <u>Section 4.4.4(b)</u> ([***] by Ionis), all Product-Specific Patents, excluding Ionis&#8217; interest in any Joint Collaboration
              Patent Rights, that are (a) Controlled by Ionis or its Affiliates on the Effective Date or at any time during the Term and (b) necessary or reasonably useful (or, with respect to patent applications, would be necessary or reasonably useful if
              such patent applications were to issue as patents) to Exploit a Licensed Product; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that Patent Rights that include only claims that are
              directed to (i) subject matter applicable to oligonucleotide compounds or products in general or (ii) an oligonucleotide compound that does not specifically modulate expression of PKK via the binding, partially or wholly, of such compound to
              RNA that encodes PKK, will not be considered Ionis Product-Specific Patents, and in each case of (i) and (ii), such Patent Rights will be considered Ionis Core Technology Patents<font style="color: rgb(0, 0, 0);">. A list of </font>Ionis
              Product-Specific Patents <font style="color: rgb(0, 0, 0);">as of the </font>Effective Date <font style="color: rgb(0, 0, 0);">is set forth on </font><font style="font-variant: small-caps;"><u>Schedule 1.103</u></font> (Ionis
              Product-Specific Patents); <font style="font-style: italic;">provided</font> that, any Patent Right existing as of the Effective Date that otherwise would be included in the definition of Ionis Product-Specific Patent but is not included on
              <font style="font-variant: small-caps;"><u>Schedule 1.103</u></font> (Ionis Product-Specific Patents) will still be considered a Ionis Product-Specific Patent<font style="color: rgb(0, 0, 0);">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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        <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.104</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product-Specific Technology</font>&#8221; means Ionis Product-Specific Know-How and Ionis Product-Specific Patents.</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.105</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product Trademarks</font>&#8221; has the meaning set forth in <u>Section 10.10.1(c)</u> (Ownership of Ionis Product Trademarks).</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.106</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Prosecuted Patent Rights</font>&#8221; has the meaning set forth in <u>Section 10.2.1(a)</u> (Right to Prosecute).</div>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.107</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Publication</font>&#8221; has the meaning set forth in <u>Section 12.5.2</u> (Ionis&#8217; Right to Publish).</div>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.108</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Regulatory Activities</font>&#8221; has the meaning set forth in <u>Section 5.1</u> (Regulatory Responsible Party).</div>
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        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.109</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Technology</font>&#8221; means the Ionis Know-How, the Ionis Patent Rights, and Ionis&#8217; interest in the Joint Collaboration Technology.</div>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.110</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Territory</font>&#8221; means worldwide, except for the Otsuka Territory.</div>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.111</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">IRS</font>&#8221; has the meaning set forth in <u>Section 9.10.3</u> (Tax Cooperation).</div>
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        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.112</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration Know-How</font>&#8221; means all Collaboration Know-How that is developed or invented jointly by a Party&#8217;s or its Affiliates&#8217;, licensees&#8217;, Sublicensees&#8217;, or
              Subcontractors&#8217; employees, agents, or independent contractors, or any Persons contractually required to assign or license such Collaboration Know-How to such Party or any Affiliate of such Party, on the one hand, and the other Party&#8217;s or its
              Affiliates&#8217;, licensees&#8217;, Sublicensees&#8217;, or Subcontractors&#8217; employees, agents, or independent contractors, or any Persons contractually required to assign or license such Collaboration Know-How to such Party or any Affiliate of such Party, on
              the other hand.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.113</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration Patent Rights</font>&#8221; means all Collaboration Patent Rights that Cover Joint Collaboration Know-How.</div>
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        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.114</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration Technology</font>&#8221; means the Joint Collaboration Know-How and the Joint Collaboration Patent Rights.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.115</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">JSC</font>&#8221; has the meaning set forth in <u>Section 8.1.1</u> (Formation and Purpose of the JSC).</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.116</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">JSC Co-Chairperson</font>&#8221; has the meaning set forth in <u>Section 8.1.2</u> (Membership).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.117</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Know-How</font>&#8221; means proprietary Inventions, discoveries, trade secrets, materials, information, experience, data, formulas, procedures, technology, and results (whether or not
              patentable), including practices, knowledge, know-how,<font style="font-weight: bold; font-style: italic;">&#160;</font>experience and test data (including physical, chemical, biological, toxicological, pharmacological, clinical and veterinary
              data), dosage regimens, assays, diagnostics, product specifications, manufacturing techniques and costs, analytical and quality control data and marketing, pricing and distribution costs, and sales practices, methods, data, and descriptions.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.118</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Knowledge</font>&#8221; means the actual knowledge, without any inquiry or investigation, of (a) with respect to Ionis, its [***]; and (b) with respect to Otsuka, its [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.119</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Licensed Compound</font>&#8221; means the GaINAc-conjugated antisense oligonucleotide compound known as donidalorsen.</div>
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        </tr>

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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.120</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Licensed Product</font>&#8221; means any pharmaceutical product that contains, comprises, or incorporates the Licensed Compound, in all current and future formulations and in any dosage
              strengths, presentations, or package configuration, and for any mode of administration. For clarity, any combination product comprised of an autoinjector pre-filled with the Licensed Compound is considered a Licensed Product. All products
              containing or comprising the same Licensed Compound, regardless of the formulation, indication, line extension or otherwise, will be considered the same Licensed Product for all purposes of this Agreement.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.121</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Losses</font>&#8221; has the meaning set forth in <u>Section 13.1</u> (Indemnification by Ionis).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.122</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">MAA</font>&#8221; or &#8220;Marketing Authorization Application&#8221; means any (a) New Drug Application as defined in the FD&amp;C Act, (b) a marketing authorization application filed with (i) the EMA
              under the centralized EMA filing procedure to gain approval to market a biopharmaceutical in the E.U., or (ii) a Regulatory Authority in any country in the E.U. if the centralized EMA filing procedure is not used to gain approval to market a
              biopharmaceutical in the E.U., or (c) substantially similar application or submission to those set forth in clause (a) or clause (b) filed with a Regulatory Authority in a country or group of countries to obtain Regulatory Approval to
              Commercialize a biopharmaceutical or diagnostic product in that country or in that group of countries, in each case ((a) through (c)), including any amendments thereto, and supplemental applications, but excluding Reimbursement Approval
              applications.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.123</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">MAA Acceptance</font>&#8221; means, with respect to a Marketing Authorization Application filed for a Licensed Product, the receipt of written notice of acceptance by the EMA of such
              Marketing Authorization Application for filing under the centralized filing procedure.</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.124</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; means, [***].</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.125</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacture</font>&#8221; means activities directed to manufacturing, processing, packaging, labeling, filling, finishing, assembly, quality assurance, quality control, testing, and release,
              shipping, or storage of any pharmaceutical or biologic product (or any components or process steps involving any 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 activities directed to Development, or Commercialization. &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing</font>&#8221; and &#8220;<font style="font-weight: bold; font-style: italic;">Manufactured</font>&#8221; will be construed accordingly.</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.126</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Costs</font>&#8221; means, with respect to a Licensed Product [***].</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.127</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Handover Date</font>&#8221; has the meaning set forth in <u>Section 7.1.2</u> (Otsuka Manufacturing).</div>
          </td>
        </tr>

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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.128</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Handover Notice</font>&#8221; has the meaning set forth in <u>Section 7.1.2</u> (Otsuka Manufacturing).</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.129</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology</font>&#8221; means any or all of (a) methods or materials used in the synthesis or analysis of an oligonucleotide or a Licensed Product regardless of sequence or
              chemical modification, (b) methods of manufacturing components of an oligonucleotide, and (c) methods or materials used in Manufacturing a Licensed Product.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.130</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology Transfer</font>&#8221; has the meaning set forth in <u>Section 7.4</u> (Manufacturing Technology Transfer).</div>
          </td>
        </tr>

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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.131</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology Transfer Agreement</font>&#8221; has the meaning set forth in <u>Section 7.4</u> (Manufacturing Technology Transfer).</div>
          </td>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.132</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Medical Affairs</font>&#8221; means activities conducted by a Party&#8217;s medical affairs department (or, if a Party does not have a medical affairs department, the equivalent function thereof),
              including real world evidence, communications with key opinion leaders, continuing medical education, symposia, advisory boards (to the extent related to medical affairs or clinical guidance), activities performed in connection with patient
              registries, review and approval of materials consistent with a Party&#8217;s or its Affiliate&#8217;s internal SOPs and Applicable Law, interactions and engagements with patient advocacy groups and other key stakeholders, and other similar medical
              programs and communications.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.133</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Milestone Events</font>&#8221; means the Regulatory Milestone Events and the Sales Milestone Events.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.134</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Milestone Payments</font>&#8221; means the Regulatory Milestone Payments and the Sales Milestone Payments.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.135</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Necessary Global In-License</font>&#8221; has the meaning set forth in <u>Section 2.7.2(a)</u> (Acquisition of Potential In-Licenses).</div>
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        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.136</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Net Sales</font>&#8221; means, with respect to any Licensed Product, the amount invoiced by Otsuka or its Affiliates or Sublicensees (each a &#8220;<font style="font-weight: bold; font-style: italic;">Selling Party</font>&#8221;) for sales of such Licensed Product in arm&#8217;s length transactions to Third Parties in all countries in the Otsuka Territory, less deduction (if not already deducted in the amount invoiced) of the following
              items with respect to sales of such Licensed Product:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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            <div>Normal and customary trade, quantity, or cash discounts to non-affiliated brokers, agents or customers to the extent actually allowed and taken, <font style="font-style: italic;">provided</font> that such discounts are not applied
              disproportionately to the Licensed Products when compared to the other products of the Selling Party, as applicable;</div>
          </td>
        </tr>

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    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
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            <div>Actual amounts repaid or credited by reason of rejections, returns, defects, price adjustments, billing errors, or trial prescriptions, including amounts repaid, discounted or credited by reason of risk sharing schemes with respect to the
              Licensed Product with any Governmental Authority;</div>
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        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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            <div>To the extent separately stated on purchase orders, invoices, or other documents of sale, any taxes, tariffs, duties, excises or other governmental charges (including any value added tax, sales tax, consumption tax or similar tax, other
              than any taxes based on income) imposed or levied on the production, sale, transportation, delivery, or use, exportation or importation of the Licensed Products;</div>
          </td>
        </tr>

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    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
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            <div>Rebates, reimbursements, fees, clawbacks, discounts or<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#160;</sup>chargeback payments paid, granted or credited to managed health care organizations, pharmacy benefit
              managers (or equivalent thereof), national, state/provincial, local, and other governments or Governmental Authorities, their agencies/purchasers/reimbursement providers (including those requested by any Governmental Authority any time after
              the actual sale of a Licensed Product), or to any Third Party payor, administrator, contractee or purchaser, including trade customers, including any fees levied by any Governmental Authority as a result of healthcare reform policies, and
              including those offered as a result of the clinical or real-world performance of the Licensed Product after it is marketed and sold;</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Outbound transportation costs prepaid or allowed and costs of insurance in transit, with the exclusion of storage and warehousing costs;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Any invoiced amounts that are not collected, including bad debts; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Any other deductions that are consistent with the Selling Party&#8217;s Accounting Standards and are not duplicative of the above deductions;</div>
          </td>
        </tr>

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    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 72pt;"><font style="font-style: italic;">provided</font> that the following deductions are not allowed in the calculation of Net Sales: (i) co-payment assistance; (ii) discounts offered to insurers to
      facilitate patient access to the product; (iii) program and data management fees paid to wholesalers/distributors; (iv) commissions paid to third-party logistics (3PL) providers; and (v) product samples shipped to indirect customers.</div>
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    <div style="text-align: justify; text-indent: 36pt; margin-left: 36pt;">If a Selling Party makes any adjustments to such deductions after the associated Net Sales have been reported pursuant to this Agreement, then the adjustments will be reported and
      reconciled with the next report and payment of any royalties due.</div>
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    <div style="text-align: justify; text-indent: 36pt; margin-left: 36pt;">Net Sales will not include (i) any payments among Selling Parties, unless such paying party is the end user of the relevant Licensed Product, (ii) any payments in consideration of
      supplies of the applicable Licensed Product for use in Clinical Trials, or (iii) payments for promotional samples, compassionate use, named-patient use, or expanded access, indigent or other patient access programs, in each case when sold or
      distributed at or below the applicable Selling Party&#8217;s costs (including supply price paid).</div>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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    <div style="text-align: justify; text-indent: 36pt; margin-left: 36pt;">If a Selling Party sells a Licensed Product in the Otsuka Territory as part of a therapy or product in combination with other pharmaceutical or biologic products, diagnostic
      products, ingredients, delivery devices or other components other than the Licensed Compound (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Other Product</font>&#8221;) whether combined in a single formulation or package, formulated or
      packaged separately but sold under a single label approved by a Regulatory Authority, packaged together for sale or shipment as a single unit, or marketed or sold collectively as a single product, but, in all cases, sold together for a single price
      (a &#8220;<font style="font-weight: bold; font-style: italic;">Combination Product</font>&#8221;), Net Sales of such Combination Product for the purposes of determining payments based on Net Sales hereunder will be calculated by multiplying actual Net Sales of
      such Combination Product as determined in the first paragraph of this Net Sales definition (&#8220;<font style="font-weight: bold; font-style: italic;">Combination Product Net Sales</font>&#8221;) by the fraction A/(A+B) where A is the average selling price of
      the Licensed Compound sold separately in such country during the applicable reporting period, and B is the sum of the average selling price(s) of the Other Product(s) in the Combination Product in such country during the same reporting period. If the
      Licensed Compound is sold separately in an applicable reporting period in a country in the Otsuka Territory, but the Other Product(s) are not sold separately in the same country in the same reporting period, then Net Sales of such Combination Product
      will be calculated by multiplying the Combination Product Net Sales by the fraction A/C where A is the average selling price of the Licensed Compound sold separately in such country during such reporting period, and C is the average selling price of
      the Combination Product in such country during such reporting period. If neither the Licensed Compound nor the Other Product(s) are sold separately in the same country in the same reporting period, then Net Sales of such Combination Product will be
      calculated by multiplying the Combination Product Net Sales by a fraction that reflects the value of the Licensed Compound relative to the value of the Other Product(s) in such Combination Product, which fraction shall be determined by Otsuka in its
      reasonable judgment, and reasonably acceptable to Ionis, and in such event, Otsuka shall provide Ionis with supporting documentation for such determination. Notwithstanding the foregoing, the Parties agree that the Licensed Product Manufactured and
      supplied by Ionis pursuant to the Supply Agreements in the form of an autoinjector pre-filled with Licensed Compound will not be subject to the terms of this paragraph, and such autoinjector will not be deemed an Other Product for purposes of
      calculating Net Sales.</div>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.137</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 4.4.4(a)</u> (Shared Costs).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd08232a48b4d48bfbe171d2c95e44e4d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.138</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 4.4.4(a)</u> (Shared Costs).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z367d9a823b70425abf7f3f244c55d465" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.139</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Non-Clinical HAE Development Plan</font>&#8221; has the meaning set forth in <u>Section 4.2.2</u> (Non-Clinical HAE Development Plan).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z79310830f12c4ea2939169b64afbada0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.140</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">OFAC</font>&#8221; means the Office of Foreign Assets Control of the United States Department of the Treasury or any successor agency thereto.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zb9969bce589b4a5292183fe72f6d650f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.141</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ongoing Cross-Territory Studies</font>&#8221; has the meaning set forth in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z4a7de9fb25f743c19d953197c0c3a992" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.142</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Opt-In Fee</font>&#8221; has the meaning set forth in <u>Section 4.4.4(c)</u> (Otsuka Opt-In).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7fb6554a74074939a8059de9feddfd62" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.143</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Opt-In Notice</font>&#8221; has the meaning set forth in <u>Section 4.4.4(c)</u> (Otsuka Opt-In).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z466ec0ccbb0847d682328ccbc5787282" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.144</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Other Covered Party</font>&#8221; means any political party or party official, or any candidate for political office.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z05af19d36390418baf4a62bde57486cf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.145</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Other Global In-License</font>&#8221; has the meaning set forth in <u>Section 2.7.2(c)</u> (Non-Approved Potential In-Licenses).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z14f55de9020b4af4ab5962c6dff28091" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.146</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Other Product</font>&#8221; has the meaning set forth in <u>Section 1.136</u> of this <u>Appendix 1</u> (Definitions).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5a7734bee8c64d2a96574454a59528ad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.147</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Collaboration Know-How</font>&#8221; has the meaning set forth in <u>Section 10.1.2(b)</u> (Ownership of Arising Intellectual Property).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z152baa04d8f6471fbd39ff8ece00469f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.148</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Collaboration Patent Rights</font>&#8221; has the meaning set forth in <u>Section 10.1.2(b)</u> (Ownership of Arising Intellectual Property).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7ad61233304546e7b6c645ce1fce5fb0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.149</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Indemnitee</font>&#8221; has the meaning set forth in <u>Section 13.1</u> (Indemnification by Ionis).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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        <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
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    <table id="z32fcc78d6ce04a6889ca56339d8dc91e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.150</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Know-How</font>&#8221; means all Collaboration Know-How (excluding Otsuka&#8217;s interest in Joint Collaboration Know-How) that is (a) Controlled by Otsuka or any of its Affiliates during
              the Term and (b) necessary or reasonably useful to Exploit a Licensed Product.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z31a98b571d9a496bad7bcae2de5cb3a7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.151</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Patent Rights</font>&#8221; means all Collaboration Patent Rights (excluding Otsuka&#8217;s interest in Joint Collaboration Patent Rights) that are (a) Controlled by Otsuka or any of its
              Affiliates during the Term and (b) necessary or reasonably useful (or, with respect to patent applications, would be necessary or reasonably useful if such patent applications were to issue as patents) to Exploit a Licensed Product.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z481261e721d1498f9a0192fc1841d8ba" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.152</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Product Trademarks</font>&#8221; has the meaning set forth in <u>Section 10.10.1(b)</u> (Ownership of Otsuka Product Trademarks).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z56223d0f545a4c71aa9fce1116ba4e9c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.153</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div> &#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Publication</font>&#8221; has the meaning set forth in <u>Section 12.5.1</u> (Otsuka&#8217;s Right to Publish).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z480b89cf20e04613bb3864ff3c7dbe1a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.154</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Technology</font>&#8221; means Otsuka Know-How, Otsuka Patent Rights, and Otsuka&#8217;s interest in the Joint Collaboration Technology.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z79aadfc475db4bc080171cf9f7a1ee00" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.155</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory</font>&#8221; means (a) all members of the European Union or the European Economic Area (EEA) as of the Effective Date, and (b) the following countries: Iceland,
              Liechtenstein, Norway, Switzerland, and the United Kingdom.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.156</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Brand Strategic and Operating Plan</font>&#8221; has the meaning set forth in <u>Section 6.5</u> (Otsuka Territory Brand Strategic and Operating Plan).</div>
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        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.157</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Medical Affairs Plan</font>&#8221; has the meaning set forth in <u>Section 6.7.2</u> (Otsuka Territory Medical Affairs Plan).</div>
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    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.158</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory-Specific Development Plan</font>&#8221; has the meaning set forth in <u>Section 4.3</u> (Otsuka Territory-Specific Development Plan).</div>
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    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.159</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Otsuka Territory Trademark Infringement</font>&#8221; has the meaning set forth in <u>Section 10.10.4(a)</u> (Unitary Product Trademark).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.160</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Packaging and Labeling</font>&#8221; means primary, secondary, or tertiary packaging and labeling of a Licensed Product (in its commercial packaging presentation) for sale or use in a
              country, including the Approved Labeling and insertion of materials such as patient inserts, patient medication guides, and professional inserts and any other written, printed, or graphic materials accompanying such Licensed Product and any
              brand security or anti-counterfeiting measures included in the packaging elements for such Licensed Product considered to be part of the finished packaged Licensed Product, and all testing and release thereof.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.161</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Party Vote</font>&#8221; has the meaning set forth in <u>Section 8.4.1</u> (General Decision-Making Process).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.162</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Patent Challenge</font>&#8221; means, with respect to a Person, that such Person contests or assists a Third Party in contesting the scope, validity, or enforceability of a Patent Right or
              any foreign counterpart thereof anywhere in the world in any court, tribunal, arbitration proceeding, or other proceeding, including the U.S. Patent and Trademark Office and the U.S. International Trade Commission. A Patent Challenge
              includes: (a) filing an action under 28 U.S.C. &#167;&#167; 2201-2202 seeking a declaration of invalidity or unenforceability of any such Patent Right; (b) filing, or joining in, a petition under 35 U.S.C. &#167; 311 to institute <font style="font-style: italic;">inter partes</font> review of any such Patent Right; (c) filing, or joining in, a petition under 35 U.S.C. &#167; 321 to institute post-grant review of any such Patent Right or any portion thereof; (d) filing or commencing any
              opposition, nullity, or similar proceedings challenging the validity of any such Patent Right in the Territory; or (e) any foreign equivalent of clauses (a), (b), (c), or (d), including any proceeding in any country or patent office in any
              country or region in the Otsuka Territory.</div>
          </td>
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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.163</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Patent Prosecution</font>&#8221; means activities directed to (a) preparing, filing, and prosecuting applications (of all types) for any Patent Right, (b) maintaining any Patent Right, and
              (c) deciding whether to abandon or maintain any Patent Right.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.164</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Patent Rights</font>&#8221; means (a) all patents, patent applications, and utility models in any country or jurisdiction, including provisional applications, priority applications, and
              international applications, (b) all patent applications filed either from such patents or patent applications or from an application claiming priority from any of these, including divisionals, continuations, and continuations-in-part, (c) any
              and all patents that have issued or in the future issue from the foregoing patent applications, (d) any and all substitutions, renewals, registrations, confirmations, revalidations, reissues, and re-examinations of the foregoing patents or
              patent applications, and (e) extensions, restorations, supplemental protection certificates, and the like based on any of the foregoing patents or patent applications.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.165</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Payment Assignment</font>&#8221; has the meaning set forth in <u>Section 16.1</u> (Assignment).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.166</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Payment Forms</font>&#8221; means one copy of each of the following documents which, at the time Ionis provides such documents to Otsuka, must be currently effective (un-expired), completed
              and signed: the United States Internal Revenue Service Form 6166 (United States Residency Certification) as received from the United States Internal Revenue Service; Form 3 (Application Form for Income Tax Convention); and Form 17 (Attachment
              Form for Limitation on Benefits Article).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.167</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Person</font>&#8221; means any corporation, limited or general partnership, limited liability company, joint venture, trust, unincorporated association, governmental body, authority, bureau,
              or agency, or any other entity or body, or an individual.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.168</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Pharmacovigilance Agreement</font>&#8221; means an agreement regarding receipt, investigation, and reporting of product complaints, adverse events, product recalls, and any other information
              related to the safety of the Licensed Products in the Territory.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.169</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Phase 3 Clinical Trial</font>&#8221; means a Clinical Trial of a Licensed Product that satisfies the requirements for a Phase 3 study as defined in 21 CFR &#167; 312.21(c) (or any amended or
              successor regulations) or that satisfies the requirements of similar laws or regulations outside the United States.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.170</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; means the [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.171</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Post-Approval Cross-Territory Mandatory Studies</font>&#8221; has the meaning set forth in <u>Section 4.2.1</u> (Cross-Territory Clinical Development Plan).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.172</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Post-Approval Mandatory Study</font>&#8221; means any Clinical Trial or other study of a pharmaceutical or biologic product initiated following receipt of Regulatory Approval or to be
              conducted after receipt of Regulatory Approval, in each case, that was mandated by the applicable Regulatory Authority in any country in the Territory as a condition of receiving or maintaining a Regulatory Approval for a product with respect
              to a particular indication in such country&#160; (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) or that is required for a label extension for a product in such country. For clarity, a [***] is a Post-Approval Mandatory Study.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.173</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Potential In-License</font>&#8221; has the meaning set forth in <u>Section 2.7.2(a)</u> (Acquisition of Potential In-Licenses).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.174</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Product Materials</font>&#8221; has the meaning set forth in <u>Section 6.9</u> (Product Materials).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.175</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Product-Specific Patents</font>&#8221; means Patent Rights Controlled by a Party or any of its Affiliates as of or after the Effective Date claiming: (a) the composition of matter of a
              Licensed Product, or (b) methods of using a Licensed Product.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.176</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Professional Requirements</font>&#8221; means (a) the codes and standards of the European Accreditation Council for Continuing Medical Education (EACCME) and the European Federation of
              Pharmaceutical Industries and Associations (EFPIA), (b) the codes of the Prescription Medicines Code of Practice Authority (PMCPA) and the Association of the British Pharmaceutical Industry (ABPI), (c) FDA&#8217;s regulations, guidance, and
              enforcement letters concerning the advertising of prescription drug products, (d) the American Medical Association&#8217;s Guidelines on Gifts to Physicians from Industry, (e) the Accreditation Council for Continuing Medical Education (ACCME)
              Standards for Commercial Support of Continuing Medical Education, (f) the Pharmaceutical Supply Chain Initiative (PSCI) and Pharmaceutical Industry Principles for Responsible Supply Chain Management, (g) the Code on Interactions with
              Healthcare Professionals promulgated by the Pharmaceutical Research and Manufacturers of America (PhRMA Code), (h) the Department of Health and Human Services Office of Inspector General Compliance Program Guidance for Pharmaceutical
              Manufacturers (OIG Compliance Guidance), and (i) all other accepted national and international pharmaceutical industry codes of practice in and for the relevant countries in the Territory, as any of the foregoing may be amended from
              time-to-time.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.177</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Publication</font>&#8221; has the meaning set forth in <u>Section 12.5</u> (Publications).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.178</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">PV Subcommittee</font>&#8221; has the meaning set forth in <u>Section 5.11</u> (Pharmacovigilance Subcommittee).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.179</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; means [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z03bc70998b704358aaf5b742a5ae8d1c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.180</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Quality Agreement</font>&#8221; has the meaning set forth in <u>Section 7.2.3</u> (Quality Agreements).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z4f71acd8c649404d9f66239dce8dea31" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.181</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Receiving Party</font>&#8221; has the meaning set forth in <u>Section 1.29</u> (Confidential Information) of this <u>Appendix 1</u> (Definitions).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.182</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Reduced Royalties</font>&#8221; has the meaning set forth in <u>Section 9.3.3</u> (Reduced Royalty Term).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.183</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Reduced Royalty Term</font>&#8221; has the meaning set forth in <u>Section 9.3.3</u> (Reduced Royalty Term).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.184</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 9.3.2(c)</u> ([***]).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.185</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Approval</font>&#8221; means, with respect to a particular country or other regulatory jurisdiction, any approval of an MAA or other approval, product, or establishment license,
              registration, or authorization of any Regulatory Authority necessary for the commercial sale of a pharmaceutical, diagnostic, or biologic product in such country or other regulatory jurisdiction, excluding, in each case, Reimbursement
              Approval.</div>
          </td>
        </tr>

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    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.186</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Authority</font>&#8221; means, in a particular country or jurisdiction, any applicable Governmental Authority involved in granting Regulatory Approval in such country or
              jurisdiction, including (a) in the U.S., the FDA and any other applicable Governmental Authority in the U.S. having jurisdiction over any pharmaceutical, diagnostic, or biologic product, (b) in the E.U., the EMA and any other applicable
              Governmental Authority in the E.U. having jurisdiction over any pharmaceutical, diagnostic, or biologic product, and (c) in other countries, other analogous Governmental Authorities having jurisdiction over any pharmaceutical, diagnostic, or
              biologic product.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.187</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Exclusivity</font>&#8221; means, with respect to a Licensed Product in a country in the Otsuka Territory, the period of time during which: (a) Otsuka or its Affiliate or
              Sublicensee has been granted the exclusive legal right by a Regulatory Authority (or is otherwise entitled to the exclusive legal right by operation of Applicable Law) in such country to market and sell such Licensed Product, and such right
              precludes a Third Party from making such Licensed Product available for purchase for any indication; or (b) the data and information submitted by Otsuka or its Affiliate or Sublicensee to the relevant Regulatory Authority in such country for
              purposes of obtaining Regulatory Approval of such Licensed Product may not be referenced, or relied upon in any way by a Third Party or such Regulatory Authority to support the Regulatory Approval or marketing of any product by a Third Party
              in such country, or if such data and information is referenced, or relied upon to support a Regulatory Approval granted to a Third Party in such country, the product may not be placed on the market for any indication.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.188</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Milestone Events</font>&#8221; has the meaning set forth in <u>Section 9.2.1</u> (Regulatory Milestones).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.189</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Milestone Payments</font>&#8221; has the meaning set forth in <u>Section 9.2.1</u> (Regulatory Milestones).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.190</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Responsible Party</font>&#8221; means the Party designated under <u>Section 5.1</u> (Regulatory Responsible Party).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.191</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Subcommittee</font>&#8221; has the meaning set forth in <u>Section 5.2</u> (Regulatory Subcommittee).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.192</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Submission</font>&#8221; means any filing, application, or submission with any Regulatory Authority in support of the Development, Manufacture, Commercialization, or other
              Exploitation of a pharmaceutical, diagnostic, or biologic product (including to obtain, support, or maintain Regulatory Approval from that Regulatory Authority), and all written or electronic correspondence or communication with or from the
              relevant Regulatory Authority, as well as minutes of any material meetings, telephone conferences, or discussions with the relevant Regulatory Authority. Regulatory Submissions include all INDs, MAAs, and other applications for Regulatory
              Approval and their equivalents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.193</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Support</font>&#8221; has the meaning set forth in <u>Section 5.6</u> (Cooperation).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.194</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Reimbursement Approval</font>&#8221; means, as applicable, (a) the Governmental Authority approval, agreement, determination, or other decision establishing prices that can be charged for a
              product in regulatory jurisdictions where the applicable Governmental Authority approves or determines the prices charged to end-users for pharmaceutical, diagnostic, or biologic products, or (b) the Governmental Authority approval,
              agreement, determination or decision establishing the prices at which a product will be reimbursed in regulatory jurisdictions where the applicable Governmental Authority approves, determines or recommends the reimbursement or use of
              pharmaceutical, diagnostic, or biologic products.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <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;" noshade="noshade"></div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.195</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Remedial Action</font>&#8221; has the meaning set forth in <u>Section 5.13.1</u> (Notification and Determination).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.196</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Representatives</font>&#8221; means, with respect to a Person, such Person&#8217;s employees, officers, directors, consultants, contractors, Subcontractors and agents, in each case, who are
              authorized to act on behalf of such Person.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zb40198eb5ced41dd9064558adb714c5a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.197</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Requested Assistance</font>&#8221; has the meaning set forth in <u>Section 3.2</u> (Technology Transfer Costs).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd598d76a93014c2584daf363702543a8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.198</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Restricted Party</font>&#8221; means any individual or entity on one or more of the Restricted Party Lists.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z45bf08efc3b94f26bcf66c091a056315" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.199</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Restricted Party List</font>&#8221; means the list of sanctioned entities maintained by the United Nations; the Specially Designated Nationals and Blocked Persons List, the Foreign Sanctions
              Evaders List and the Sectoral Sanctions Identifications List, all administered by OFAC; the U.S. Denied Persons List, the U.S. Entity List, and the U.S. Unverified List, all administered by the U.S. Department of Commerce; and the entities
              subject to restrictive measures and the consolidated list of Persons, Groups, and Entities Subject to E.U. Financial Sanctions, as implemented by the E.U. Common Foreign &amp; Security Policy.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5791e14ddd714ae38d426886678106ba" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.200</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Reversion License</font>&#8221; has the meaning set forth in <u>Section 14.9.2(a)</u> (License Grant).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z1d09c9ee87bd4c9ca88f5e00c4df3c6d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.201</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Review Period</font>&#8221; has the meaning set forth in <u>Section 12.5.1</u> (Otsuka&#8217;s Right to Publish).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zfad80070bf554f42a467b4cdda0c60fe" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.202</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">ROFN Exercise Notice</font>&#8221; has the meaning set forth in <u>Section 2.8.1</u> (ROFN Exercise).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z3736c1f06da34158a987399e331c0834" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.203</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">ROFN Negotiation Period</font>&#8221; has the meaning set forth in <u>Section 2.8.2</u> (Negotiation).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z4cb5a76c01d74e718c866590f0f57696" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.204</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">ROFN Notice and Package</font>&#8221; has the meaning set forth in <u>Section 2.8.1</u> (ROFN Exercise).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z643e192d281844a28c15499e8833caf9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.205</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Royalties</font>&#8221; has the meaning set forth in <u>Section </u><u>9.3.3</u> (Reduced Royalty Term).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd5a52fcaae0b4092bfb16e70297ce47a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.206</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Royalty Report</font>&#8221; has the meaning set forth in <u>Section </u><u>9.3.4(b)</u> (Royalty Report).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z7d104e40c5784d169f9b6b96ead60bb4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.207</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Royalty Term</font>&#8221; has the meaning set forth in <u>Section </u><u>9.3.3</u> (Reduced Royalty Term).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc4f0f9ebf58e4a489f6dc5a1028106e5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.208</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 9.3.1</u> (Royalty Payments During the Initial Royalty Term).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zdce7c6bad0334cdcb346903017e33d43" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.209</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Rules</font>&#8221; has the meaning set forth in <u>Section 15.2.2</u> (Arbitration).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z951c82ca2d6d4f98869f04866f3df219" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.210</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Sales Milestone Events</font>&#8221; has the meaning set forth in <u>Section </u><u>9.2.2</u> (Sales Milestones).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z6f8b74976aa1479887e254d5f66fbcd1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.211</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Sales Milestone Payments</font>&#8221; has the meaning set forth in <u>Section </u><u>9.2.2</u> (Sales Milestones).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z78fe6a059f584fd78879566b8c563052" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.212</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Selling Party</font>&#8221; has the meaning set forth in <u>Section 1.136</u> (Net Sales) of this <u>Appendix 1</u> (Definitions).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zbdedf43a848b48c5a8a7dfd2afedf3b7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.213</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 4.4.1(c)</u> (Shared Development Costs).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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        <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.214</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Shared Cross-Territory Development Costs</font>&#8221; has the meaning set forth in <u>Section 4.4.1(c)</u> (Shared Development Costs).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z849513ecce1d40c4bcd58728ba213ba7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.215</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Shared Development Budget</font>&#8221; has the meaning set forth in <u>Section 4.4.2(a)</u> (Shared Development Budget).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.216</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Subcommittee</font>&#8221; has the meaning set forth in <u>Section 8.2.1</u> (Formation; Authority).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z420f2ff5dd5e4247942e3e729f405df6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.217</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Subcommittee Co-Chairperson</font>&#8221; has the meaning set forth in <u>Section 8.2.2</u> (Subcommittee Leadership and Meetings).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.218</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Subcontractors</font>&#8221; has the meaning set forth in <u>Section 2.3.2</u> (Right to Subcontract).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.219</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Sublicensee</font>&#8221; means, with respect to a Party, any Third Party to which such Party or its Affiliate grants a sublicense under any of the rights licensed to the applicable Party
              under this Agreement other than a Subcontractor.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.220</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Supply Agreements</font>&#8221; has the meaning set forth in <u>Section 7.2.2</u> (Commercial Supply Agreement).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.221</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Tax</font>&#8221; or &#8220;<font style="font-weight: bold;">Taxes</font>&#8221; means any present or future taxes, levies, imposts, duties, charges, assessments or fees of any nature (including any
              interest thereon), including value add, sales, excise or similar taxes.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.222</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Technology Transfer</font>&#8221; has the meaning set forth in <u>Section 3.1</u> (Initial Know-How Transfer).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.223</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Term</font>&#8221; has the meaning set forth in <u>Section 14.1</u> (Term).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z0a40b2783d894090908694f8442b239a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.224</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Territory</font>&#8221; means (a) the Otsuka Territory, with respect to Otsuka, (b) the Ionis Territory, with respect to Ionis, and (c) collectively, worldwide.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z0645c9a8fe2147228c604bf9a16f3f60" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.225</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party</font>&#8221; means any Person other than a Party or its Affiliates.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zf2df5ef541f54c4c84a34d554876db80" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.226</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Claims</font>&#8221; has the meaning set forth in <u>Section 13.1</u> (Indemnification by Ionis).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zb5b6719f58054903b9979753fbc7c632" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.227</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section 2.8.2</u> (Negotiation).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="ze9a9f7799c9c4865865c29d4238da38a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.228</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Patent Challenge</font>&#8221; has the meaning set forth in <u>Section 10.4</u> (Defense of Third Party Patent Challenges).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z93226c7600b44a5fb7db89800dca4579" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.229</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Payments</font>&#8221; means, with respect to a Licensed Product, any (a) payments (including upfront payments, milestone payments, license fees, royalties and monetary damages)
              made by Otsuka or its Affiliate to a Third Party (i) pursuant to an agreement between Otsuka or its Affiliate and such Third Party entered into following the Effective Date in accordance with <u>Section 2.7.2</u> (Potential In-Licenses) to
              obtain rights to Patent Rights or Know-How from such Third Party that would be infringed or misappropriated by the Exploitation of a Licensed Product in the Otsuka Territory or (ii) pursuant to an agreement between Otsuka or its Affiliate and
              such Third Party, or otherwise, as part of a settlement or to satisfy a judgment in accordance with <u>Section 10.5.3</u> (Settlement), or (b) amounts for which Otsuka reimburses Ionis under a Collaboration In-License, in each case ((a) or
              (b)), that are directly in consideration for or reasonably allocable to a license or sublicense (as applicable) to Otsuka or its Affiliate under, or are paid in settlement or to satisfy a judgment of a claim relating to, Patent Rights or
              Know-How Controlled by such Third Party that would, but for a license thereunder, be infringed or misappropriated by the Exploitation of such Licensed Product.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <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;" noshade="noshade"></div>
    </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.230</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Trademark</font>&#8221; means any word, name, symbol, color, shape, designation or any combination thereof, including any trademark, service mark, trade name, brand name, sub-brand name,
              domain name, trade dress, product configuration, program name, delivery form name, certification mark, collective mark, logo, tagline, slogan, design or business symbol, that functions as an identifier of source or origin, whether or not
              registered and all statutory and common law rights therein and all registrations and applications therefor, together with all goodwill associated with, or symbolized by, any of the foregoing.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.231</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Trademark Infringement Suit</font>&#8221; has the meaning set forth in <u>Section 10.10.5(a)</u> (Unitary Product Trademark).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z4e32e5281a5c4c85953c8fa69dd16a82" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.232</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Transition Plan</font>&#8221; has the meaning set forth in <u>Section 14.9.3(a)</u> (Scope).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd0c236094e5449059b4ec4df58552aa5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.233</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Transition Services</font>&#8221; has the meaning set forth in <u>Section 14.9.3(a)</u> (Scope).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zd7b9cb5775304a5f9d4c6e8f3830f019" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.234</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Unitary Product Trademark</font>&#8221; has the meaning set forth in <u>Section 10.10.1(a)</u> (Unitary Product Trademark).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zab34c879c8c8457d902bc75c5fd8e5ad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.235</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Upfront Payment</font>&#8221; has the meaning set forth in <u>Section </u><u>9.1</u> (Upfront Payment).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.236</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">U.S.</font>&#8221; means the United States of America (including all possessions and territories thereof, including Puerto Rico).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.237</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">U.S. Dollars</font>&#8221; or &#8220;<font style="font-weight: bold;">$</font>&#8221; means the legal tender of the U.S.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="z5bdeed6f84e34bacbc7269fc8dede44a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.238</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Valid Claim</font>&#8221; means a claim of an issued and unexpired patent (as may be adjusted through a patent term adjustment or extended through supplementary protection certificate or
              patent term extension or the like) that has not been revoked, held invalid, or held unenforceable by a patent office or other Governmental Authority of competent jurisdiction in a final and non-appealable judgment (or judgment from which no
              appeal was taken within the allowable time period), and [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table id="zc49d4b2b8a784ae6900e06ff5fd1ae5c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.239</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Withheld Amount</font>&#8221; has the meaning set forth in <u>Section 9.10.2</u> (Withholding Tax).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <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;" noshade="noshade"></div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 1.49</u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Existing Third-Party IP Agreements</div>
    <div>&#160;</div>
    <div>[***]</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 style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 1.91</u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Ionis Core Technology Patents</div>
    <div>&#160;</div>
    <table id="zff0152765850401480fc6d0f35e1b546" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 18%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Ionis File No.</div>
          </td>
          <td style="width: 14.82%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Country/Treaty</div>
          </td>
          <td style="width: 17.58%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Application No./</div>
            <div style="text-align: center; font-weight: bold;">Patent No.</div>
          </td>
          <td style="width: 12.72%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Filing Date</div>
          </td>
          <td style="width: 13.12%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Grant Date</div>
          </td>
          <td style="width: 22.51%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Title</div>
          </td>
        </tr>
        <tr>
          <td style="width: 18%; vertical-align: middle; 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: 14.82%; vertical-align: middle; 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: 17.58%; vertical-align: middle; 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: 12.72%; vertical-align: middle; 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: 13.12%; vertical-align: middle; 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: 22.51%; vertical-align: middle; 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: 18%; vertical-align: middle; 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: 14.82%; vertical-align: middle; 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: 17.58%; vertical-align: middle; 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: 12.72%; vertical-align: middle; 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>
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          <td style="width: 13.12%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 22.51%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 17.58%; vertical-align: middle; 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>
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          <td style="width: 12.72%; vertical-align: middle; 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>
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          <td style="width: 22.51%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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            <div style="text-align: center;">[***]</div>
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          <td style="width: 14.82%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 17.58%; vertical-align: middle; 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>
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          <td style="width: 12.72%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 22.51%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 18%; vertical-align: middle; 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>
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          <td style="width: 14.82%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 17.58%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 12.72%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 22.51%; vertical-align: middle; 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>
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          <td style="width: 18%; vertical-align: middle; 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>
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          <td style="width: 14.82%; vertical-align: middle; 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>
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          <td style="width: 17.58%; vertical-align: middle; 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>
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          <td style="width: 12.72%; vertical-align: middle; 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>
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          <td style="width: 22.51%; 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);">
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          <td style="width: 18%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 14.82%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 17.58%; vertical-align: middle; 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>
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          <td style="width: 12.72%; vertical-align: middle; 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: 13.12%; vertical-align: middle; 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: 22.51%; 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>
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          <td style="width: 18%; vertical-align: middle; 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>
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          <td style="width: 14.82%; vertical-align: middle; 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>
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          <td style="width: 17.58%; vertical-align: middle; 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>
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          <td style="width: 12.72%; vertical-align: middle; 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>
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          <td style="width: 22.51%; 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);">
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          <td style="width: 17.58%; vertical-align: middle; 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>
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          <td style="width: 12.72%; vertical-align: middle; 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>
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          <td style="width: 13.12%; vertical-align: middle; 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>
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          <td style="width: 22.51%; 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>
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          <td style="width: 18%; vertical-align: middle; 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>
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          <td style="width: 14.82%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 17.58%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 12.72%; vertical-align: middle; 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>
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          <td style="width: 22.51%; 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);">
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          <td style="width: 18%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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          <td style="width: 13.12%; vertical-align: middle; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
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            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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: 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;">[***]</div>
          </td>
          <td style="width: 14.82%; 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: center;">[***]</div>
          </td>
          <td style="width: 17.58%; 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: 12.72%; 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: 13.12%; 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: 22.51%; 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><br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <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;" noshade="noshade"></div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 1.96</u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Ionis Manufacturing and Analytical Patents</div>
    <div>&#160;</div>
    <table id="zc4c323eee4d348629f166cb8adbfc420" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 18%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Ionis File No.</div>
          </td>
          <td style="width: 23.49%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Country</div>
          </td>
          <td style="width: 16.67%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Application No./</div>
            <div style="text-align: center; font-weight: bold;">Patent No.</div>
          </td>
          <td style="width: 11.37%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Filing Date</div>
          </td>
          <td style="width: 11.37%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Grant Date</div>
          </td>
          <td style="width: 19.71%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Title</div>
          </td>
        </tr>
        <tr>
          <td style="width: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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: 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;">[***]</div>
          </td>
          <td style="width: 23.49%; 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: 16.67%; 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: 11.37%; 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: 11.37%; 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: 19.71%; 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><br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <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;" noshade="noshade"></div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 1.103</u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Ionis Product-Specific Patents</div>
    <div>&#160;</div>
    <table id="z7ee5b09377554701934f61bbe18943d5" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 15.47%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Ionis File No.</div>
          </td>
          <td style="width: 12.21%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Country/</div>
            <div style="text-align: center; font-weight: bold;">Treaty</div>
          </td>
          <td style="width: 9.09%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Status</div>
          </td>
          <td style="width: 16.77%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Application No./</div>
            <div style="text-align: center; font-weight: bold;">Patent No.</div>
          </td>
          <td style="width: 11.11%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Filing Date</div>
          </td>
          <td style="width: 11.65%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Grant Date</div>
          </td>
          <td style="width: 23.69%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Title</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</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 style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
    </div>
    <table id="z37bd43c373394a77bca718c69526f0eb" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 15.47%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1" nowrap="nowrap">Ionis File No.</td>
          <td style="width: 12.21%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center;" rowspan="1">
            <div style="font-weight: bold;">Country/</div>
            <div style="font-weight: bold;">Treaty</div>
          </td>
          <td style="width: 9.09%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">Status</td>
          <td style="width: 16.77%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center;" rowspan="1">
            <div style="font-weight: bold;">Application No./</div>
            <div style="font-weight: bold;">Patent No.</div>
          </td>
          <td style="width: 11.11%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">Filing Date</td>
          <td style="width: 11.65%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center; font-weight: bold;" rowspan="1">Grant Date</td>
          <td style="width: 23.69%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1" nowrap="nowrap">Title</td>
        </tr>
        <tr>
          <td style="width: 15.47%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 16.77%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</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 style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
    </div>
    <table id="z96d3fcf928704c92a9f224149e902d73" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 15.47%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1" nowrap="nowrap">Ionis File No.</td>
          <td style="width: 12.21%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">
            <div>Country/</div>
            <div>Treaty</div>
          </td>
          <td style="width: 9.09%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">Status</td>
          <td style="width: 16.77%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">
            <div>Application No./</div>
            <div>Patent No.</div>
          </td>
          <td style="width: 11.11%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">Filing Date</td>
          <td style="width: 11.65%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">Grant Date</td>
          <td style="width: 23.69%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1" nowrap="nowrap">Title</td>
        </tr>
        <tr>
          <td style="width: 15.47%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.09%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 16.77%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.11%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.65%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 23.69%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</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 style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
    </div>
    <table id="z025bbbfea71d40a99b2864f629f10e76" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 15.47%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1" nowrap="nowrap">Ionis File No.</td>
          <td style="width: 12.21%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">
            <div>Country/</div>
            <div>Treaty</div>
          </td>
          <td style="width: 9.09%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">Status</td>
          <td style="width: 16.77%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">
            <div>Application No./</div>
            <div>Patent No.</div>
          </td>
          <td style="width: 11.11%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">Filing Date</td>
          <td style="width: 11.65%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1">Grant Date</td>
          <td style="width: 23.69%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold; text-align: center;" rowspan="1" nowrap="nowrap">Title</td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 15.47%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 12.21%; 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: 9.09%; 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: 16.77%; 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: 11.11%; 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: 11.65%; 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: 23.69%; 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);" nowrap="nowrap">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>

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    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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        <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" noshade="noshade"></div>
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    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 4.2.1</u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Cross-Territory Clinical Development Plan</div>
    <div>&#160;</div>
    <div style="text-align: center;">[***]</div>
    <div style="text-align: center;"> <br>
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    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <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;" noshade="noshade"></div>
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    <div style="text-align: center; font-weight: bold;"><font style="font-variant: small-caps;"><u>Schedule</u></font><u> 4.2.2</u></div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">Non-Clinical HAE Development Plan</div>
    <div>&#160;</div>
    <div style="text-align: center;">[***]</div>
    <div style="text-align: center;"> <br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <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;" noshade="noshade"></div>
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    <div style="text-align: center; font-weight: bold;"><font style="font-variant: small-caps;"><u>&#160;Schedule</u></font><u> 4.4.2</u></div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">Shared Development Budget</div>
    <div>&#160;</div>
    <div style="text-align: center;">[***]</div>
    <div style="text-align: center;"> <br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <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;" noshade="noshade"></div>
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    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>Schedule 14.9.3</u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Transition Services</div>
    <div>&#160;</div>
    <div style="text-align: center;">[***]</div>
    <div style="text-align: justify;"> <br>
    </div>
    <div style="text-align: justify;"><br>
      <hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"></div>
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<DOCUMENT>
<TYPE>EX-21.1
<SEQUENCE>5
<FILENAME>exhibit21-1.htm
<DESCRIPTION>EXHIBIT 21.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 23.9.1.5178
         Copyright 1995 - 2024 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:f499a0ae-02f9-48a9-add8-20f1dcaf844d"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit&#160;21.1</div><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; 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', Times, serif; font-size: 10pt;">&#160;</div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics, Inc., a Delaware Corporation</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics Canada Inc., a Canadian Corporation</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics Germany GmbH, a German Corporation</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics UK Limited, a United Kingdom Limited Private Company</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; 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', Times, serif; font-size: 10pt;">Akcea Therapeutics Italia S.r.l., an Italian Company</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea Therapeutics Portugal, Unipessoal Lda, a Portuguese Company</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis Faraday LLC, a Delaware Corporation</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis Gazelle LLC, a Delaware Corporation</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis Ireland Limited, an Irish Private Company</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis USA Limited, a United Kingdom Limited Private Company</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Osprey Therapeutics, Inc., a Delaware Corporation</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis Development (Ireland) Limited, an Irish Private Company</div><div><br></div><div style="text-align: left;"><br></div><div><br></div><div><br></div></div></body></html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-23.1
<SEQUENCE>6
<FILENAME>exhibit23-1.htm
<DESCRIPTION>EXHIBIT 23.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 23.9.1.5178
         Copyright 1995 - 2024 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; 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;"><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, 333-242382, and&#160; 333-275741) 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, 333-258503, and 333-273902) of Ionis Pharmaceuticals, Inc. of our reports dated February 21, 2024, 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, 2023.</div><div style="text-align: left;"><br></div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z8dc2e7ad9e894966b5e118951675fa6e"><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 21, 2024</div></td><td style="width: 49.43%; vertical-align: top;">&#160;</td></tr></table><div style="text-align: left;"><br></div></div></body></html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-31.1
<SEQUENCE>7
<FILENAME>exhibit31-1.htm
<DESCRIPTION>EXHIBIT 31.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 23.9.1.5178
         Copyright 1995 - 2024 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:27688458-8a95-448c-9822-a3a5e0da6065"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit 31.1</div><div><br></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">I, Brett P. Monia, certify that:</div><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z436048bdc396420e8e4316070d34cc48"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; 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;">I have reviewed this Annual Report on Form 10-K of Ionis Pharmaceuticals, Inc.;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zd756e36ad24144c39340d970d3718632"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on my knowledge, this annual report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this annual report;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z1dd09feab6d74fcc8bbf658f05febdf3"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on my knowledge, the consolidated financial statements, and other financial information included in this annual report, fairly present in all material respects the financial condition, consolidated results of operations and consolidated cash flows of the registrant as of, and for, the periods presented in this annual report;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z4126035c3347472c87c738d5b582f2d7"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The registrant&#8217;s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z93b85ec1cc094c71bff51a1b0a55f8a4"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z54550e279dd24dcdad2698c34ed2f549"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">b)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, 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;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z56490ec554b44a1e8570ba3c57178ad0"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">c)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Evaluated the effectiveness of the registrant&#8217;s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z5a2bce60c7e44a70806cbd5644407e6d"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">d)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Disclosed in this report any change in the registrant&#8217;s internal control over financial reporting that occurred during the registrant&#8217;s most recent fiscal quarter (the registrant&#8217;s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant&#8217;s internal control over financial reporting; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z648c98cfcbe043f6af77b8f2c45128c6"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The registrant&#8217;s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant&#8217;s auditors and the audit committee of registrant&#8217;s board of directors (or persons performing the equivalent functions):</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zebefe8c225fc42049a245367e1e07923"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant&#8217;s ability to record, process, summarize and report financial information; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zaa39a0c9f219446ab4e9f08a1a256906"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">b)</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 fraud, whether or not material, that involves management or other employees who have a significant role in the registrant&#8217;s internal control over financial reporting.</div></td></tr></table><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;&#160;</div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z315be44e8b1b4667b8bca4c8bed11672"><tr><td style="width: 41.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dated: February 21, 2024</div></td><td style="width: 58.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 58.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.41%; 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><td style="width: 58.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.41%; 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><td style="width: 58.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.41%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Executive Officer</div></td><td style="width: 58.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr></table><div><br></div></div></body></html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-31.2
<SEQUENCE>8
<FILENAME>exhibit31-2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 23.9.1.5178
         Copyright 1995 - 2024 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:f325a129-9b94-442a-a705-509884803066"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit 31.2</div><div><br></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">I, Elizabeth L. Hougen, certify that:</div><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z5a4d4cb3a0d041589dff5b7f673b094a"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; 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;">I have reviewed this Annual Report on Form 10-K of Ionis Pharmaceuticals, Inc.;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z44651f18ce93483796364ec674db265a"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on my knowledge, this annual report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this annual report;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zdab9d8873a0c4319bbec1748e3b2f42b"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on my knowledge, the consolidated financial statements, and other financial information included in this annual report, fairly present in all material respects the financial condition, consolidated results of operations and consolidated cash flows of the registrant as of, and for, the periods presented in this annual report;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zbc95c31333a440288053e6330c096cbc"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The registrant&#8217;s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zc7444b00a83d4c5c9701b058a576fe1f"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; 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color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z3d3f80500f4d4ea2b8235094ad543e7a"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">c)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Evaluated the effectiveness of the registrant&#8217;s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z13d19d27de5b4b39977ceddccf5ed34c"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">d)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Disclosed in this report any change in the registrant&#8217;s internal control over financial reporting that occurred during the registrant&#8217;s most recent fiscal quarter (the registrant&#8217;s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant&#8217;s internal control over financial reporting; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zdf60783ac7a2471286269db0fa979493"><tr><td style="width: 27pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The registrant&#8217;s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant&#8217;s auditors and the audit committee of registrant&#8217;s board of directors (or persons performing the equivalent functions):</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z38479254be38445d903e86fa8ae51e97"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a)</div></td><td style="width: auto; vertical-align: top;"><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant&#8217;s ability to record, process, summarize and report financial information; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z209801372671476e8d6655282d4a4e9b"><tr><td style="width: 45pt; vertical-align: top; text-align: right;"><div style="text-align: left; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">b)</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 fraud, whether or not material, that involves management or other employees who have a significant role in the registrant&#8217;s internal control over financial reporting.</div></td></tr></table><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;&#160;</div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z02f5d900385e4da989606e60e6937485"><tr><td style="width: 41.23%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dated: February 21, 2024</div></td><td style="width: 58.77%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.23%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 58.77%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.23%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ELIZABETH L. HOUGEN</div></td><td style="width: 58.77%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.23%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elizabeth L. Hougen</div></td><td style="width: 58.77%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 41.23%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Financial Officer</div></td><td style="width: 58.77%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr></table><div><br></div></div></body></html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-32
<SEQUENCE>9
<FILENAME>exhibit32-1.htm
<DESCRIPTION>EXHIBIT 32.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 23.9.1.5178
         Copyright 1995 - 2024 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:6efc6d20-d43f-45b4-aa04-090d35475d75"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit 32.1</div><div><br></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CERTIFICATION</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 requirement set forth in Rule&#160;13a-14(b)&#160;of the Securities Exchange Act of 1934, as amended (the &#8220;Exchange Act&#8221;), and Section&#160;1350 of Chapter 63 of Title 18 of the United States Code (18&#160;U.S.C. &#167;1350),&#160; Brett P. Monia, the Chief Executive Officer of Ionis Pharmaceuticals, Inc., (the &#8220;Company&#8221;), and Elizabeth L. Hougen, the Chief Financial Officer of the Company, each hereby certifies that, to the best of his or her knowledge:</div><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z87a6e2bd462241bf887a31ff497bce10"><tr><td style="width: 18pt;"></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;">The Company&#8217;s Annual Report on Form 10-K for the year ended December 31, 2023, to which this Certification is attached as Exhibit 32.1 (the &#8220;Annual Report&#8221;), fully complies with the requirements of Section 13(a) or Section 15(d) of the Securities Exchange Act of 1934, as amended; and</div></td></tr></table><div><br></div><table style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z5eca1f0ea95943239fe9a94000730aa8"><tr><td style="width: 18pt;"></td><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;">The information contained in the Annual Report fairly presents, in all material respects, the financial condition of the Company at the end of the period covered by the Annual Report and the results of operations of the Company for the period covered by the Annual Report.</div></td></tr></table><div><br></div><div><br></div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z83210d77cd044802b88a773f654dc1df"><tr><td style="width: 40.1%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a name="z67c7d4b1a5524f7095e3a56b8ca645e7"><!--Anchor--></a>Dated: February 21, 2024</div></td><td style="width: 9.69%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 40.28%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 9.92%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 40.1%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 9.69%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 40.28%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 9.92%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 40.1%; 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><td style="width: 9.69%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 40.28%; vertical-align: top; border-bottom: #000000 2px solid;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ELIZABETH L. HOUGEN</div></td><td style="width: 9.92%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 40.1%; 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><td style="width: 9.69%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 40.28%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elizabeth L. Hougen</div></td><td style="width: 9.92%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 40.1%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Executive Officer</div></td><td style="width: 9.69%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 40.28%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Financial Officer</div></td><td style="width: 9.92%; vertical-align: top;">&#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;">A signed original of this written statement required by Section 906 has been provided to Ionis Pharmaceuticals, Inc. and will be retained by Ionis Pharmaceuticals, Inc. and furnished to the Securities and Exchange Commission or its staff upon request.</div><div><br></div><div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">This certification accompanies the Form&#160;10-K to which it relates, is not deemed filed with the Securities and Exchange Commission and is not to be incorporated by reference into any filing of Ionis Pharmaceuticals,&#160;Inc. under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended (whether made before or after the date of the Form&#160;10-K), irrespective of any general incorporation language contained in such filing.</div><div><br></div></div></body></html>
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<DOCUMENT>
<TYPE>EX-97
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<FILENAME>exhibit97.htm
<DESCRIPTION>EXHIBIT 97
<TEXT>
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    <div style="text-align: right; font-weight: normal;">Exhibit 97</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc. </div>
    <div style="text-indent: 35.15pt; margin-right: 119.2pt; margin-left: 130.9pt; font-variant: small-caps; font-weight: bold;"> <br>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Amended and Restated Clawback Policy</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"> <br>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="zca8b30fda8d844a6af3e36bef139e78e" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 35.95pt; vertical-align: top; font-weight: bold;">1.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-variant: small-caps; font-weight: bold;">Introduction</div>
          </td>
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    </table>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">The Board of Directors (the &#8220;<font style="font-weight: bold; font-style: italic;">Board</font>&#8221;) of Ionis Pharmaceuticals, Inc., a Delaware corporation (the &#8220;<font style="font-weight: bold; font-style: italic;">Company</font>&#8221;), has determined that it is in the best interests of the Company and its stockholders to adopt this Amended and Restated Clawback Policy (this &#8220;<font style="font-weight: bold; font-style: italic;">Policy</font>&#8221;)

      providing for the Company&#8217;s recoupment of Recoverable Incentive Compensation that is received by Covered Officers of the Company under certain circumstances. Certain capitalized terms used in this Policy have the meanings given to such terms in
      Section 3 below.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">This Policy is designed to comply with, and shall be interpreted to be consistent with, Section 10D of the Exchange Act, Rule 10D-1 promulgated thereunder (&#8220;<font style="font-weight: bold; font-style: italic;">Rule 10D-1</font>&#8221;) and Nasdaq Listing Rule 5608 (the &#8220;<font style="font-weight: bold; font-style: italic;">Listing Standards</font>&#8221;). This Policy amends and restates in its entirety that certain Clawback Policy, made
      effective March 23, 2021, previously adopted by the Board.</div>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z82816535a2704d049cdf981afd477e3b" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 35.95pt; vertical-align: top; font-weight: bold;">2.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-variant: small-caps; font-weight: bold;">Effective Date</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">This Policy shall apply to all Incentive Compensation that is received by a Covered Officer on or after October 2, 2023 (the &#8220;<font style="font-weight: bold; font-style: italic;">Effective Date</font>&#8221;).

      Incentive Compensation is deemed &#8220;<font style="font-weight: bold; font-style: italic;">received</font>&#8221; in the Company&#8217;s fiscal period in which the Financial Reporting Measure specified in the Incentive Compensation award is attained, even if the
      payment or grant of such Incentive Compensation occurs after the end of that period.</div>
    <div>&#160;</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="zdc4317c507424bfd8bb71d60290dc2ab" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 35.95pt; vertical-align: top; font-weight: bold;">3.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-variant: small-caps; font-weight: bold;">Definitions</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Accounting Restatement</font>&#8221; means an accounting restatement that the Company is required to prepare due to the material noncompliance of the
      Company with any financial reporting requirement under the securities laws, including any required accounting restatement to correct an error in previously issued financial statements that is material to the previously issued financial statements, or
      that would result in a material misstatement if the error were corrected in the current period or left uncorrected in the current period.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Accounting Restatement Date</font>&#8221; means the earlier to occur of (a) the date that the Board, a committee of the Board authorized to take such
      action, or the officer or officers of the Company authorized to take such action if Board action is not required, concludes, or reasonably should have concluded, that the Company is required to prepare an Accounting Restatement, or (b) the date that
      a court, regulator or other legally authorized body directs the Company to prepare an Accounting Restatement.</div>
    <div style="text-indent: 36pt;">&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Administrator</font>&#8221; means the Nominating, Governance and Review Committee of the Board or, in the absence of such committee, the Board. The
      Nominating, Governance and Review Committee of the Board will confer with the Compensation Committee of the Board on matters related to enforcement of this Policy.</div>
    <div style="text-indent: 36pt;">&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Code</font>&#8221; means the U.S. Internal Revenue Code of 1986, as amended, and the regulations promulgated thereunder.</div>
    <div style="text-indent: 36pt;">&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Compensation Committee</font>&#8221; means the Compensation Committee of the Board.</div>
    <div style="text-indent: 36pt;"> <br>
    </div>
    <div style="text-indent: 36pt;"> &#8220;<font style="font-weight: bold; font-style: italic;">Covered Officer</font>&#8221; means each current and former Executive Officer.</div>
    <div style="text-indent: 36pt;"> <br>
    </div>
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    <div style="text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Exchange</font>&#8221; means The Nasdaq Stock Market LLC.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Exchange Act</font>&#8221; means the U.S. Securities Exchange Act of 1934, as amended.</div>
    <div style="text-indent: 36pt;">&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Executive Officer</font>&#8221; means each individual who is currently or was previously designated as an &#8220;officer&#8221; of the Company as defined in Rule
      16a-1(f) of the Exchange Act.</div>
    <div style="text-indent: 36pt;">&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Financial Reporting Measures</font>&#8221; means measures that are determined and presented in accordance with the accounting principles used in
      preparing the Company&#8217;s financial statements, and any measures derived wholly or in part from such measures, including Company stock price and total stockholder return (&#8220;<font style="font-weight: bold; font-style: italic;">TSR</font>&#8221;). A measure
      need not be presented in the Company&#8217;s financial statements or included in a filing with the SEC in order to be a Financial Reporting Measure.</div>
    <div style="text-indent: 36pt;">&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Incentive Compensation</font>&#8221; means any compensation that is granted, earned or vested based wholly or in part upon the attainment of a
      Financial Reporting Measure.</div>
    <div style="text-indent: 36pt;">&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Lookback Period</font>&#8221; means the three completed fiscal years immediately preceding the Accounting Restatement Date, as well as any transition
      period (resulting from a change in the Company&#8217;s fiscal year) within or immediately following those three completed fiscal years (except that a transition period of at least nine months shall count as a completed fiscal year). Notwithstanding the
      foregoing, the Lookback Period shall not include fiscal years completed prior to the Effective Date.</div>
    <div style="text-indent: 36pt;">&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">Recoverable Incentive Compensation</font>&#8221; means Incentive Compensation received by a Covered Officer during the Lookback Period that exceeds the
      amount of Incentive Compensation that would have been received had such amount been determined based on the Accounting Restatement, computed without regard to any taxes paid (<font style="font-style: italic;">i.e.</font>, on a gross basis without
      regarding to tax withholdings and other deductions). For any compensation plans or programs that take into account Incentive Compensation, the amount of Recoverable Incentive Compensation for purposes of this Policy shall include, without limitation,
      the amount contributed to any notional account based on Recoverable Incentive Compensation and any earnings to date on that notional amount. For any Incentive Compensation that is based on stock price or TSR, where the Recoverable Incentive
      Compensation is not subject to mathematical recalculation directly from the information in an Accounting Restatement, the Administrator will determine the amount of Recoverable Incentive Compensation based on a reasonable estimate of the effect of
      the Accounting Restatement on the stock price or TSR upon which the Incentive Compensation was received. The Company shall maintain documentation of the determination of that reasonable estimate and provide such documentation to the Exchange in
      accordance with the Listing Standards.</div>
    <div style="text-indent: 36pt;">&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<font style="font-weight: bold; font-style: italic;">SEC</font>&#8221; means the U.S. Securities and Exchange Commission.</div>
    <div>&#160;</div>
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          <td style="width: 35.95pt; vertical-align: top; font-weight: bold;">4.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-weight: bold;">RECOUPMENT</div>
          </td>
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    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">Applicability of Policy. </font>This Policy applies to Incentive Compensation received by a Covered Officer (i)
      after beginning services as an Executive Officer, (ii) who served as an Executive Officer at any time during the performance period for such Incentive Compensation, (iii) while the Company had a class of securities listed on a national securities
      exchange or a national securities association, and (iv) during the Lookback Period.</div>
    <div style="text-indent: 36pt;">&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(b)</font>&#160;&#160;&#160; &#160;&#160;&#160; <font style="font-weight: bold;">Recoupment Generally. </font>Pursuant to the provisions of this Policy, if there is an Accounting Restatement,
      the Company must reasonably promptly recoup the full amount of the Recoverable Incentive Compensation, unless the conditions of one or more subsections of Section 4(c) of this Policy are met and the Compensation Committee, or, if such committee does
      not consist solely of independent directors, a majority of the independent directors serving on the Board, has made a determination that recoupment would be impracticable. Recoupment is required regardless of whether the Covered Officer engaged in
      any misconduct and regardless of fault, and the Company&#8217;s obligation to recoup Recoverable Incentive Compensation is not dependent on whether or when any restated financial statements are filed.</div>
    <div style="text-align: justify; text-indent: 36pt;"> <br>
    </div>
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      <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: rgb(0, 0, 0); font-weight: normal; font-style: normal;">2</font></div>
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    <div>
      <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: rgb(0, 0, 0);" class="DSPFListTable" id="z92fe40e3a68d4de2a637ee67c65d3a9a" cellpadding="0" cellspacing="0">

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            <td style="width: 36pt;">&#160;</td>
            <td style="width: 36pt; vertical-align: top; font-weight: bold;">(c)</td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Impracticability of Recovery. </font>Recoupment may be determined to be impracticable if, and only if:</div>
            </td>
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    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 36pt;">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; the direct expense paid to a third party to assist in enforcing this Policy would exceed the amount of the applicable Recoverable Incentive Compensation; provided that,
      before concluding that it would be impracticable to recover any amount of Recoverable Incentive Compensation based on expense of enforcement, the Company shall make a reasonable attempt to recover such Recoverable Incentive Compensation, document
      such reasonable attempt(s) to recover, and provide that documentation to the Exchange in accordance with the Listing Standards; or</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 36pt;"> <br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 36pt;">(ii)&#160;&#160;&#160;&#160;&#160;&#160;&#160; recoupment of the applicable Recoverable Incentive Compensation would likely cause an otherwise tax-qualified retirement plan, under which benefits are broadly
      available to employees of the Company, to fail to meet the requirements of Code Section 401(a)(13) or Code Section 411(a) and regulations thereunder.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160; &#160; &#160; <font style="font-weight: bold;">Sources of Recoupment. </font>To the extent permitted by applicable law, the Administrator shall, in its sole
      discretion, determine the timing and method for recouping Recoverable Incentive Compensation hereunder, provided that such recoupment is undertaken reasonably promptly. The Administrator may, in its discretion, seek recoupment from a Covered Officer
      from any of the following sources or a combination thereof, whether the applicable compensation was approved, awarded, granted, payable or paid to the Covered Officer prior to, on or after the Effective Date: (i) direct repayment of Recoverable
      Incentive Compensation previously paid to the Covered Officer; (ii) cancelling prior cash or equity-based awards (whether vested or unvested and whether paid or unpaid); (iii) cancelling or offsetting against any planned future cash or equity-based
      awards; (iv) forfeiture of deferred compensation, subject to compliance with Code Section 409A; and (v) any other method authorized by applicable law or contract. Subject to compliance with any applicable law, the Administrator may effectuate
      recoupment under this Policy from any amount otherwise payable to the Covered Officer, including amounts payable to such individual under any otherwise applicable Company plan or program, <font style="font-style: italic;">e.g.</font>, base salary,
      bonuses or commissions and compensation previously deferred by the Covered Officer. The Administrator need not utilize the same method of recovery for all Covered Officers or with respect to all types of Recoverable Incentive Compensation.</div>
    <div style="text-align: justify; text-indent: 36pt;"> <br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-weight: bold;">No Indemnification of Covered Officers. </font>Notwithstanding any indemnification agreement, applicable
      insurance policy or any other agreement or provision of the Company&#8217;s certificate of incorporation or bylaws to the contrary, no Covered Officer shall be entitled to indemnification or advancement of expenses in connection with any enforcement of
      this Policy by the Company, including paying or reimbursing such Covered Officer for insurance premiums to cover potential obligations to the Company under this Policy.</div>
    <div style="text-align: justify; text-indent: 36pt;"> <br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">(f)</font>&#160;&#160;&#160;&#160;&#160; &#160;&#160; <font style="font-weight: bold;">Indemnification of Administrator. </font>Any members of the Administrator, and any other members of the Board
      who assist in the administration of this Policy, shall not be personally liable for any action, determination or interpretation made with respect to this Policy and shall be indemnified by the Company to the fullest extent under applicable law and
      Company policy with respect to any such action, determination or interpretation. The foregoing sentence shall not limit any other rights to indemnification of the members of the Board under applicable law or Company policy.</div>
    <div style="text-align: justify;"> <br>
    </div>
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      <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; color: rgb(0, 0, 0); font-weight: normal; font-style: normal;">3</font></div>
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    <div style="text-align: justify; text-indent: 36pt;">Except as specifically set forth herein, this Policy shall be administered by the Administrator. The Administrator shall have full and final authority to make any and all determinations required
      under this Policy. Any determination by the Administrator with respect to this Policy shall be final, conclusive and binding on all interested parties and need not be uniform with respect to each individual covered by this Policy. In carrying out the
      administration of this Policy, the Administrator is authorized and directed to consult with the full Board or such other committees of the Board as may be necessary or appropriate as to matters within the scope of such other committee&#8217;s
      responsibility and authority. Subject to applicable law, the Administrator may authorize and empower any officer or employee of the Company to take any and all actions that the Administrator, in its sole discretion, deems necessary or appropriate to
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    <div style="text-align: justify; text-indent: 36pt;">If any provision of this Policy or the application of any such provision to a Covered Officer shall be adjudicated to be invalid, illegal or unenforceable in any respect, such invalidity, illegality
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    <div style="text-align: justify; text-indent: 36pt;">Nothing contained in this Policy, and no recoupment or recovery as contemplated herein, shall limit any claims, damages or other legal remedies the Company or any of its affiliates may have against a
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      Financial Officer and to any other compensation recoupment policy and/or similar provisions in any employment, equity plan, equity award, or other individual agreement, to which the Company is a party or which the Company has adopted or may adopt and
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    <div style="text-align: justify; text-indent: 36pt;">The Administrator may amend, terminate or replace this Policy or any portion of this Policy at any time and from time to time in its sole discretion. The Administrator shall amend this Policy as it
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    <div style="text-align: justify; text-indent: 36pt;">This Policy shall be binding and enforceable against all Covered Officers and, to the extent required by Rule 10D-1 and/or the applicable Listing Standards, their beneficiaries, heirs, executors,
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    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc. </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"> <br>
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    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">Amended and Restated Clawback Policy</div>
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    <div style="text-align: justify;">I, the undersigned, agree and acknowledge that I am bound by, and subject to, the Ionis Pharmaceuticals, Inc. Amended and Restated Clawback Policy, as may be amended, restated, supplemented or otherwise modified from
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    <div style="text-align: justify;">In the event that the Administrator (as defined in the Policy) determines that any compensation granted, awarded, earned or paid to me must be forfeited or reimbursed to the Company pursuant to the Policy, I will
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      <link:roleType roleURI="http://ionispharma.com/role/StockholdersEquityTables" id="StockholdersEquityTables">
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      <link:roleType roleURI="http://ionispharma.com/role/IncomeTaxesTables" id="IncomeTaxesTables">
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        <link:usedOn>link:calculationLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/FourthQuarterFinancialDataUnauditedTables" id="FourthQuarterFinancialDataUnauditedTables">
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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>
        <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>
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</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.LAB
<SEQUENCE>14
<FILENAME>ions-20231231_lab.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by Broadridge PROfile 23.12.1.5186 Broadridge-->
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesAuthorized" xlink:to="us-gaap_CommonStockSharesAuthorized_lbl2" xlink:title="label: CommonStockSharesAuthorized to us-gaap_CommonStockSharesAuthorized_lbl2" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesIssued_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_CommonStockSharesIssued_lbl1" xml:lang="en-US" id="us-gaap_CommonStockSharesIssued_lbl1">Common stock, shares issued (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesIssued" xlink:to="us-gaap_CommonStockSharesIssued_lbl1" xlink:title="label: CommonStockSharesIssued to us-gaap_CommonStockSharesIssued_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesIssued" xlink:to="us-gaap_CommonStockSharesIssued_lbl2" xlink:title="label: CommonStockSharesIssued to us-gaap_CommonStockSharesIssued_lbl2" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesOutstanding_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_CommonStockSharesOutstanding_lbl1" xml:lang="en-US" id="us-gaap_CommonStockSharesOutstanding_lbl1">Common stock, shares outstanding (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesOutstanding" xlink:to="us-gaap_CommonStockSharesOutstanding_lbl1" xlink:title="label: CommonStockSharesOutstanding to us-gaap_CommonStockSharesOutstanding_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesOutstanding_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockSharesOutstanding_lbl2" xml:lang="en-US" id="us-gaap_CommonStockSharesOutstanding_lbl2">Common Stock, Shares, Outstanding</link:label>
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract" xlink:label="DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract" xlink:title="DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtCurrent" xlink:to="us-gaap_ConvertibleDebtCurrent_lbl1" xlink:title="label: ConvertibleDebtCurrent to us-gaap_ConvertibleDebtCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock_lbl" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesPolicyTextBlock_lbl1">Cost of Goods and Service [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.xsd#us-gaap_DebtDisclosureTextBlock" xlink:label="DebtDisclosureTextBlock" xlink:title="DebtDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_DebtDisclosureTextBlock_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="DebtDisclosureTextBlock" xlink:to="us-gaap_DebtDisclosureTextBlock_lbl" xlink:title="label: DebtDisclosureTextBlock to us-gaap_DebtDisclosureTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_DebtDisclosureTextBlock_lbl1">Debt Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtDisclosureTextBlock" xlink:to="us-gaap_DebtDisclosureTextBlock_lbl1" xlink:title="label: DebtDisclosureTextBlock to us-gaap_DebtDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="DebtInstrumentCarryingAmount" xlink:title="DebtInstrumentCarryingAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentCarryingAmount_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentCarryingAmount_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentCarryingAmount_lbl">Outstanding principal balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentCarryingAmount" xlink:to="us-gaap_DebtInstrumentCarryingAmount_lbl" xlink:title="label: DebtInstrumentCarryingAmount to us-gaap_DebtInstrumentCarryingAmount_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentFaceAmount" xlink:label="DebtInstrumentFaceAmount" xlink:title="DebtInstrumentFaceAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentFaceAmount_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount_lbl">Face amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentFaceAmount" xlink:to="us-gaap_DebtInstrumentFaceAmount_lbl" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_DebtInstrumentFaceAmount_lbl1" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount_lbl1">Face amount of offering</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentFaceAmount" xlink:to="us-gaap_DebtInstrumentFaceAmount_lbl1" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentFaceAmount_lbl2" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount_lbl2">Debt Instrument, Face Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentFaceAmount" xlink:to="us-gaap_DebtInstrumentFaceAmount_lbl2" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage" xlink:label="DebtInstrumentInterestRateEffectivePercentage" xlink:title="DebtInstrumentInterestRateEffectivePercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl">Effective interest rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateEffectivePercentage" xlink:to="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" xlink:title="label: DebtInstrumentInterestRateEffectivePercentage to us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1">Debt Instrument, Interest Rate, Effective Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentInterestRateEffectivePercentage" xlink:to="us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" xlink:title="label: DebtInstrumentInterestRateEffectivePercentage to us-gaap_DebtInstrumentInterestRateEffectivePercentage_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DeferredTaxLiabilitiesOther" xlink:label="DeferredTaxLiabilitiesOther" xlink:title="DeferredTaxLiabilitiesOther" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredTaxLiabilitiesOther_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DeferredTaxLiabilitiesOther_lbl1" xml:lang="en-US" id="us-gaap_DeferredTaxLiabilitiesOther_lbl1">Deferred Tax Liabilities, Other</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DefinedContributionPlanCostRecognized" xlink:label="DefinedContributionPlanCostRecognized" xlink:title="DefinedContributionPlanCostRecognized" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xml:lang="en-US" id="us-gaap_AllocatedShareBasedCompensationExpense_lbl1">Share-Based Payment Arrangement, Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AllocatedShareBasedCompensationExpense" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xlink:title="label: AllocatedShareBasedCompensationExpense to us-gaap_AllocatedShareBasedCompensationExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeStockMember_lbl1" xml:lang="en-US" id="us-gaap_EmployeeStockMember_lbl1">Employee Stock [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_lbl1" xlink:title="label: EmployeeStockMember to us-gaap_EmployeeStockMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensation" xlink:label="ShareBasedCompensation" xlink:title="ShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensation_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensation_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensation_lbl">Stock-based compensation expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensation" xlink:to="us-gaap_ShareBasedCompensation_lbl" xlink:title="label: ShareBasedCompensation to us-gaap_ShareBasedCompensation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensation_lbl1">Share-Based Payment Arrangement, Noncash Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensation" xlink:to="us-gaap_ShareBasedCompensation_lbl1" xlink:title="label: ShareBasedCompensation to us-gaap_ShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationAbstract" xlink:label="ShareBasedCompensationAbstract" xlink:title="ShareBasedCompensationAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationAbstract_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAbstract_lbl">Stock-Based Compensation [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_ShareBasedCompensationAbstract_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAbstract_lbl1">Stock-Based Compensation Expense [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAbstract" xlink:to="us-gaap_ShareBasedCompensationAbstract_lbl1" xlink:title="label: ShareBasedCompensationAbstract to us-gaap_ShareBasedCompensationAbstract_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAbstract_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationAbstract_lbl2" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAbstract_lbl2">Share-Based Payment Arrangement, Noncash Expense [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAbstract" xlink:to="us-gaap_ShareBasedCompensationAbstract_lbl2" xlink:title="label: ShareBasedCompensationAbstract to us-gaap_ShareBasedCompensationAbstract_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_lbl">Maximum percentage of employee compensation used to purchase shares</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Maximum Employee Subscription Rate</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EntityWideRevenueMajorCustomerLineItems" xlink:label="EntityWideRevenueMajorCustomerLineItems" xlink:title="EntityWideRevenueMajorCustomerLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EntityWideRevenueMajorCustomerLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EntityWideRevenueMajorCustomerLineItems_lbl" xml:lang="en-US" id="us-gaap_EntityWideRevenueMajorCustomerLineItems_lbl">Revenue, Major Customer [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityWideRevenueMajorCustomerLineItems" xlink:to="us-gaap_EntityWideRevenueMajorCustomerLineItems_lbl" xlink:title="label: EntityWideRevenueMajorCustomerLineItems to us-gaap_EntityWideRevenueMajorCustomerLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:label="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:title="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_lbl">Schedule of Revenue by Major Customers, by Reporting Segments [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable" xlink:to="us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_lbl" xlink:title="label: ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable to us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquitySecuritiesMember" xlink:label="EquitySecuritiesMember" xlink:title="EquitySecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesMember_lbl">Equity Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesMember" xlink:to="us-gaap_EquitySecuritiesMember_lbl" xlink:title="label: EquitySecuritiesMember to us-gaap_EquitySecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesMember_lbl1">Equity Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesMember" xlink:to="us-gaap_EquitySecuritiesMember_lbl1" xlink:title="label: EquitySecuritiesMember to us-gaap_EquitySecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueOfFinancialInstrumentsPolicy" xlink:label="FairValueOfFinancialInstrumentsPolicy" xlink:title="FairValueOfFinancialInstrumentsPolicy" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueOfFinancialInstrumentsPolicy_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FairValueOfFinancialInstrumentsPolicy_lbl" xml:lang="en-US" id="us-gaap_FairValueOfFinancialInstrumentsPolicy_lbl">Fair Value Measurements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FairValueOfFinancialInstrumentsPolicy" xlink:to="us-gaap_FairValueOfFinancialInstrumentsPolicy_lbl" xlink:title="label: FairValueOfFinancialInstrumentsPolicy to us-gaap_FairValueOfFinancialInstrumentsPolicy_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueOfFinancialInstrumentsPolicy_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueOfFinancialInstrumentsPolicy_lbl1" xml:lang="en-US" id="us-gaap_FairValueOfFinancialInstrumentsPolicy_lbl1">Fair Value of Financial Instruments, Policy [Policy Text Block]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FurnitureAndFixturesMember" xlink:label="FurnitureAndFixturesMember" xlink:title="FurnitureAndFixturesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FurnitureAndFixturesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_FurnitureAndFixturesMember_lbl" xml:lang="en-US" id="us-gaap_FurnitureAndFixturesMember_lbl">Furniture and Fixtures [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FurnitureAndFixturesMember" xlink:to="us-gaap_FurnitureAndFixturesMember_lbl" xlink:title="label: FurnitureAndFixturesMember to us-gaap_FurnitureAndFixturesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_FurnitureAndFixturesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FurnitureAndFixturesMember_lbl1" xml:lang="en-US" id="us-gaap_FurnitureAndFixturesMember_lbl1">Furniture and Fixtures [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="FurnitureAndFixturesMember" xlink:to="us-gaap_FurnitureAndFixturesMember_lbl1" xlink:title="label: FurnitureAndFixturesMember to us-gaap_FurnitureAndFixturesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GainLossOnDispositionOfAssets" xlink:label="GainLossOnDispositionOfAssets" xlink:title="GainLossOnDispositionOfAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainLossOnDispositionOfAssets_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_GainLossOnDispositionOfAssets_lbl" xml:lang="en-US" id="us-gaap_GainLossOnDispositionOfAssets_lbl">Non-cash losses related to disposal of property, plant and equipment</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_GainLossOnDispositionOfAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GainLossOnDispositionOfAssets_lbl1" xml:lang="en-US" id="us-gaap_GainLossOnDispositionOfAssets_lbl1">Gain (Loss) on Disposition of Property Plant Equipment, Excluding Oil and Gas Property and Timber Property</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnDispositionOfAssets" xlink:to="us-gaap_GainLossOnDispositionOfAssets_lbl1" xlink:title="label: GainLossOnDispositionOfAssets to us-gaap_GainLossOnDispositionOfAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GainLossOnInvestments" xlink:label="GainLossOnInvestments" xlink:title="GainLossOnInvestments" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnInvestments" xlink:to="us-gaap_GainLossOnInvestments_lbl1" xlink:title="label: GainLossOnInvestments to us-gaap_GainLossOnInvestments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt" xlink:label="GainsLossesOnExtinguishmentOfDebt" xlink:title="GainsLossesOnExtinguishmentOfDebt" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxReconciliationOtherAdjustments_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncomeTaxReconciliationOtherAdjustments_lbl" xml:lang="en-US" id="us-gaap_IncomeTaxReconciliationOtherAdjustments_lbl">Other</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxReconciliationOtherAdjustments" xlink:to="us-gaap_IncomeTaxReconciliationOtherAdjustments_lbl" xlink:title="label: IncomeTaxReconciliationOtherAdjustments to us-gaap_IncomeTaxReconciliationOtherAdjustments_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxReconciliationOtherAdjustments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeTaxReconciliationOtherAdjustments_lbl1" xml:lang="en-US" id="us-gaap_IncomeTaxReconciliationOtherAdjustments_lbl1">Effective Income Tax Rate Reconciliation, Other Adjustments, Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxReconciliationOtherAdjustments" xlink:to="us-gaap_IncomeTaxReconciliationOtherAdjustments_lbl1" xlink:title="label: IncomeTaxReconciliationOtherAdjustments to us-gaap_IncomeTaxReconciliationOtherAdjustments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes" xlink:label="IncomeTaxReconciliationPriorYearIncomeTaxes" xlink:title="IncomeTaxReconciliationPriorYearIncomeTaxes" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes_lbl" xml:lang="en-US" id="us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes_lbl">Deferred tax true-up</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxReconciliationPriorYearIncomeTaxes" xlink:to="us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes_lbl" xlink:title="label: IncomeTaxReconciliationPriorYearIncomeTaxes to us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes_lbl1" xml:lang="en-US" id="us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes_lbl1">Effective Income Tax Rate Reconciliation, Prior Year Income Taxes, Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxReconciliationPriorYearIncomeTaxes" xlink:to="us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes_lbl1" xlink:title="label: IncomeTaxReconciliationPriorYearIncomeTaxes to us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes" xlink:label="IncomeTaxReconciliationStateAndLocalIncomeTaxes" xlink:title="IncomeTaxReconciliationStateAndLocalIncomeTaxes" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_lbl" xml:lang="en-US" id="us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_lbl">State income tax net of federal benefit</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxReconciliationStateAndLocalIncomeTaxes" xlink:to="us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_lbl" xlink:title="label: IncomeTaxReconciliationStateAndLocalIncomeTaxes to us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_lbl1" xml:lang="en-US" id="us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_lbl1">Effective Income Tax Rate Reconciliation, State and Local Income Taxes, Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxReconciliationStateAndLocalIncomeTaxes" xlink:to="us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_lbl1" xlink:title="label: IncomeTaxReconciliationStateAndLocalIncomeTaxes to us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxReconciliationTaxCredits" xlink:label="IncomeTaxReconciliationTaxCredits" xlink:title="IncomeTaxReconciliationTaxCredits" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxReconciliationTaxCredits_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_IncomeTaxReconciliationTaxCredits_lbl" xml:lang="en-US" id="us-gaap_IncomeTaxReconciliationTaxCredits_lbl">Tax credits</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxReconciliationTaxCredits" xlink:to="us-gaap_IncomeTaxReconciliationTaxCredits_lbl" xlink:title="label: IncomeTaxReconciliationTaxCredits to us-gaap_IncomeTaxReconciliationTaxCredits_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxReconciliationTaxCredits_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeTaxReconciliationTaxCredits_lbl1" xml:lang="en-US" id="us-gaap_IncomeTaxReconciliationTaxCredits_lbl1">Effective Income Tax Rate Reconciliation, Tax Credit, Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxReconciliationTaxCredits" xlink:to="us-gaap_IncomeTaxReconciliationTaxCredits_lbl1" xlink:title="label: IncomeTaxReconciliationTaxCredits to us-gaap_IncomeTaxReconciliationTaxCredits_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.xsd#us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:label="IncreaseDecreaseInOtherOperatingAssets" xlink:title="IncreaseDecreaseInOtherOperatingAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl">Other current and long-term 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_lbl" xlink:title="label: IncreaseDecreaseInOtherOperatingAssets to us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl" />
    <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/2023/elts/us-gaap-2023.xsd#us-gaap_InterestExpense" xlink:label="InterestExpense" xlink:title="InterestExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestExpense_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_InterestExpense_lbl" xml:lang="en-US" id="us-gaap_InterestExpense_lbl">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_lbl" xlink:title="label: InterestExpense to us-gaap_InterestExpense_lbl" />
    <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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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>
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    <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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.xsd#us-gaap_InventoryWorkInProcess" xlink:label="InventoryWorkInProcess" xlink:title="InventoryWorkInProcess" />
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    <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/2023/elts/us-gaap-2023.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" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/terseLabel" xlink:title="us-gaap_LandMember_lbl" xml:lang="en-US" id="us-gaap_LandMember_lbl">Undeveloped Land in Carlsbad, California [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LandMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LandMember_lbl1" xml:lang="en-US" id="us-gaap_LandMember_lbl1">Land [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
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    <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/2023/elts/us-gaap-2023.xsd#us-gaap_Liabilities" xlink:label="Liabilities" xlink:title="Liabilities" />
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    <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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/terseLabel" xlink:title="us-gaap_LongTermLoansFromBank_lbl" xml:lang="en-US" id="us-gaap_LongTermLoansFromBank_lbl">Long-term obligations</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermLoansFromBank_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermLoansFromBank_lbl1" xml:lang="en-US" id="us-gaap_LongTermLoansFromBank_lbl1">Loans Payable to Bank, Noncurrent</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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">2024</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>
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    <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">2028</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" />
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    <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" />
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    <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">2026</link:label>
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    <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>
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    <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">2025</link:label>
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    <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" />
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    <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/2023/elts/us-gaap-2023.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebt" xlink:to="us-gaap_LongTermDebt_lbl" xlink:title="label: LongTermDebt to us-gaap_LongTermDebt_lbl" />
    <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/2023/elts/us-gaap-2023.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingFacilityMember" xlink:to="us-gaap_ManufacturingFacilityMember_lbl" xlink:title="label: ManufacturingFacilityMember to us-gaap_ManufacturingFacilityMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaturitiesOfLongTermDebtAbstract" xlink:to="us-gaap_MaturitiesOfLongTermDebtAbstract_lbl" xlink:title="label: MaturitiesOfLongTermDebtAbstract to us-gaap_MaturitiesOfLongTermDebtAbstract_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl">Net cash provided by (used in) financing activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" xlink:title="label: NetCashProvidedByUsedInFinancingActivities to us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xlink:title="label: NetCashProvidedByUsedInFinancingActivities to us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl">Financing activities:</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1">Net Cash Provided by (Used in) Financing Activities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetCashProvidedByUsedInFinancingActivitiesAbstract" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" xlink:title="label: NetCashProvidedByUsedInFinancingActivitiesAbstract to us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl">Net cash provided by (used in) investing activities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivities_lbl1">Net Cash Provided by (Used in) Investing Activities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract_lbl">Investing activities:</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInOperatingActivities_lbl1">Net Cash Provided by (Used in) Operating Activities</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/2023/elts/us-gaap-2023.xsd#us-gaap_Revenues" xlink:label="Revenues" xlink:title="Revenues" />
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAssetsCurrent" xlink:to="us-gaap_OtherAssetsCurrent_lbl" xlink:title="label: OtherAssetsCurrent to us-gaap_OtherAssetsCurrent_lbl" />
    <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>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OtherLiabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherLiabilities_lbl" xml:lang="en-US" id="us-gaap_OtherLiabilities_lbl">Other obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherLiabilities" xlink:to="us-gaap_OtherLiabilities_lbl" xlink:title="label: OtherLiabilities to us-gaap_OtherLiabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherLiabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherLiabilities_lbl1" xml:lang="en-US" id="us-gaap_OtherLiabilities_lbl1">Other Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherLiabilities" xlink:to="us-gaap_OtherLiabilities_lbl1" xlink:title="label: OtherLiabilities to us-gaap_OtherLiabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="OtherNonoperatingIncomeExpense" xlink:title="OtherNonoperatingIncomeExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNonoperatingIncomeExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherNonoperatingIncomeExpense_lbl" xml:lang="en-US" id="us-gaap_OtherNonoperatingIncomeExpense_lbl">Other income (expense)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherNonoperatingIncomeExpense" xlink:to="us-gaap_OtherNonoperatingIncomeExpense_lbl" xlink:title="label: OtherNonoperatingIncomeExpense to us-gaap_OtherNonoperatingIncomeExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNonoperatingIncomeExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherNonoperatingIncomeExpense_lbl1" xml:lang="en-US" id="us-gaap_OtherNonoperatingIncomeExpense_lbl1">Other Nonoperating Income (Expense)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherNonoperatingIncomeExpense" xlink:to="us-gaap_OtherNonoperatingIncomeExpense_lbl1" xlink:title="label: OtherNonoperatingIncomeExpense to us-gaap_OtherNonoperatingIncomeExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:label="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:title="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PreferredStockSharesAuthorized" xlink:label="PreferredStockSharesAuthorized" xlink:title="PreferredStockSharesAuthorized" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PreferredStockSharesAuthorized_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PreferredStockSharesAuthorized_lbl" xml:lang="en-US" id="us-gaap_PreferredStockSharesAuthorized_lbl">Preferred stock, shares authorized (in shares)</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PreferredStockSharesIssued" xlink:label="PreferredStockSharesIssued" xlink:title="PreferredStockSharesIssued" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PreferredStockSharesIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_PreferredStockSharesIssued_lbl" xml:lang="en-US" id="us-gaap_PreferredStockSharesIssued_lbl">Preferred stock, shares issued (in shares)</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PreferredStockSharesOutstanding" xlink:label="PreferredStockSharesOutstanding" xlink:title="PreferredStockSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PreferredStockSharesOutstanding_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_PreferredStockSharesOutstanding_lbl" xml:lang="en-US" id="us-gaap_PreferredStockSharesOutstanding_lbl">Preferred stock, shares outstanding (in shares)</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_PreferredStockSharesOutstanding_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PreferredStockSharesOutstanding_lbl1" xml:lang="en-US" id="us-gaap_PreferredStockSharesOutstanding_lbl1">Preferred Stock, Shares Outstanding</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:label="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl" xml:lang="en-US" id="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl">Proceeds from sale of short-term investments</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProceedsFromConvertibleDebt" xlink:label="ProceedsFromConvertibleDebt" xlink:title="ProceedsFromConvertibleDebt" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment" xlink:label="ProceedsFromSaleOfPropertyPlantAndEquipment" xlink:title="ProceedsFromSaleOfPropertyPlantAndEquipment" />
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    <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>
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    <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>
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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>
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    <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: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>
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    <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/2023/elts/us-gaap-2023.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>
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    <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/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="PaymentsToAcquirePropertyPlantAndEquipment" xlink:title="PaymentsToAcquirePropertyPlantAndEquipment" />
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract" xlink:label="PaymentsToAcquirePropertyPlantAndEquipmentAbstract" xlink:title="PaymentsToAcquirePropertyPlantAndEquipmentAbstract" />
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" xlink:label="TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" xlink:title="TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Number of Shares Available for Grant</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Outstanding, Intrinsic Value</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SupplementalCashFlowInformationAbstract" xlink:to="us-gaap_SupplementalCashFlowInformationAbstract_lbl1" xlink:title="label: SupplementalCashFlowInformationAbstract to us-gaap_SupplementalCashFlowInformationAbstract_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" xlink:label="UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" xlink:title="UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions_lbl1" xml:lang="en-US" id="us-gaap_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions_lbl1">Unrecognized Tax Benefits, Decrease Resulting from Prior Period Tax Positions</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" xlink:label="UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" xlink:title="UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" xlink:label="UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" xlink:title="UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" xlink:label="UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" xlink:title="UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" xlink:to="us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate_lbl" xlink:title="label: UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate to us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PublicUtilitiesInventoryTypeDomain" xlink:label="PublicUtilitiesInventoryTypeDomain" xlink:title="PublicUtilitiesInventoryTypeDomain" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PublicUtilitiesInventoryTypeDomain" xlink:to="us-gaap_PublicUtilitiesInventoryTypeDomain_lbl" xlink:title="label: PublicUtilitiesInventoryTypeDomain to us-gaap_PublicUtilitiesInventoryTypeDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PublicUtilitiesInventoryAxis" xlink:label="PublicUtilitiesInventoryAxis" xlink:title="PublicUtilitiesInventoryAxis" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PublicUtilitiesInventoryAxis" xlink:to="us-gaap_PublicUtilitiesInventoryAxis_lbl" xlink:title="label: PublicUtilitiesInventoryAxis to us-gaap_PublicUtilitiesInventoryAxis_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1">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_lbl1" xlink:title="label: WeightedAverageNumberOfDilutedSharesOutstanding to us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" />
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    <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:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockMember" xlink:label="CommonStockMember" xlink:title="CommonStockMember" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BuildingAndBuildingImprovementsMember" xlink:label="BuildingAndBuildingImprovementsMember" xlink:title="BuildingAndBuildingImprovementsMember" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel1Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueInputsLevel1Member_lbl1" xml:lang="en-US" id="us-gaap_FairValueInputsLevel1Member_lbl1">Fair Value, Inputs, Level 1 [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_FairValueInputsLevel2Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_FairValueInputsLevel2Member_lbl1" xml:lang="en-US" id="us-gaap_FairValueInputsLevel2Member_lbl1">Fair Value, Inputs, Level 2 [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance" xlink:label="CommonStockCapitalSharesReservedForFutureIssuance" xlink:title="CommonStockCapitalSharesReservedForFutureIssuance" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl" xml:lang="en-US" id="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl">Common shares reserved for future issuance (in shares)</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtPolicyTextBlock" xlink:label="DebtPolicyTextBlock" xlink:title="DebtPolicyTextBlock" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_DebtPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_DebtPolicyTextBlock_lbl1">Debt, Policy [Policy Text Block]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockholdersEquity" xlink:label="StockholdersEquity" xlink:title="StockholdersEquity" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquity_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_StockholdersEquity_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquity_lbl1">Balance</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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquity_lbl2" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_StockholdersEquity_lbl2" xml:lang="en-US" id="us-gaap_StockholdersEquity_lbl2">Balance</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_lbl2" xlink:title="label: StockholdersEquity to us-gaap_StockholdersEquity_lbl2" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance" xlink:label="IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance" xlink:title="IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeTaxExpenseBenefit" xlink:label="IncomeTaxExpenseBenefit" xlink:title="IncomeTaxExpenseBenefit" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:label="AdditionalPaidInCapitalMember" xlink:title="AdditionalPaidInCapitalMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AdditionalPaidInCapitalMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdditionalPaidInCapitalMember_lbl" xml:lang="en-US" id="us-gaap_AdditionalPaidInCapitalMember_lbl">Additional Paid in Capital [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RetainedEarningsMember" xlink:label="RetainedEarningsMember" xlink:title="RetainedEarningsMember" />
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:label="AccumulatedOtherComprehensiveIncomeMember" xlink:title="AccumulatedOtherComprehensiveIncomeMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AccumulatedOtherComprehensiveIncomeMember_lbl" xml:lang="en-US" id="us-gaap_AccumulatedOtherComprehensiveIncomeMember_lbl">Accumulated Other Comprehensive Loss [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain" xlink:label="EquityComponentDomain" xlink:title="EquityComponentDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquityComponentDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquityComponentDomain_lbl" xml:lang="en-US" id="us-gaap_EquityComponentDomain_lbl">Equity Component [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityComponentDomain" xlink:to="us-gaap_EquityComponentDomain_lbl" xlink:title="label: EquityComponentDomain to us-gaap_EquityComponentDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl" />
    <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/2023/elts/us-gaap-2023.xsd#us-gaap_RealizedInvestmentGainsLosses" xlink:label="RealizedInvestmentGainsLosses" xlink:title="RealizedInvestmentGainsLosses" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RealizedInvestmentGainsLosses_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_RealizedInvestmentGainsLosses_lbl" xml:lang="en-US" id="us-gaap_RealizedInvestmentGainsLosses_lbl">Loss (gain) on investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RealizedInvestmentGainsLosses" xlink:to="us-gaap_RealizedInvestmentGainsLosses_lbl" xlink:title="label: RealizedInvestmentGainsLosses to us-gaap_RealizedInvestmentGainsLosses_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RealizedInvestmentGainsLosses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RealizedInvestmentGainsLosses_lbl1" xml:lang="en-US" id="us-gaap_RealizedInvestmentGainsLosses_lbl1">Realized Investment Gains (Losses)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RealizedInvestmentGainsLosses" xlink:to="us-gaap_RealizedInvestmentGainsLosses_lbl1" xlink:title="label: RealizedInvestmentGainsLosses to us-gaap_RealizedInvestmentGainsLosses_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="StockIssuedDuringPeriodSharesNewIssues" xlink:title="StockIssuedDuringPeriodSharesNewIssues" />
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:label="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="StockIssuedDuringPeriodSharesShareBasedCompensation" />
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1">Shares Issued, Shares, Share-Based Payment Arrangement, after Forfeiture</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_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised" xlink:label="StockIssuedDuringPeriodSharesStockOptionsExercised" xlink:title="StockIssuedDuringPeriodSharesStockOptionsExercised" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl">Exercised (in shares)</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_lbl" xlink:title="label: StockIssuedDuringPeriodSharesStockOptionsExercised to us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl" />
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementDisclosureTextBlock" xlink:label="CollaborativeArrangementDisclosureTextBlock" xlink:title="CollaborativeArrangementDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl">Collaborative Arrangements and Licensing Agreements</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1">Collaborative Arrangement Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementDisclosureTextBlock" xlink:to="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xlink:title="label: CollaborativeArrangementDisclosureTextBlock to us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl" />
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    <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" />
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    <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" />
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    <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" />
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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: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:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_lbl" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharesIssued" xlink:label="SharesIssued" xlink:title="SharesIssued" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_SharesIssued_lbl" xml:lang="en-US" id="us-gaap_SharesIssued_lbl">Balance (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_SharesIssued_lbl1" xml:lang="en-US" id="us-gaap_SharesIssued_lbl1">Balance (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharesIssued" xlink:to="us-gaap_SharesIssued_lbl1" xlink:title="label: SharesIssued to us-gaap_SharesIssued_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharesIssued_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharesIssued_lbl2" xml:lang="en-US" id="us-gaap_SharesIssued_lbl2">Shares, Issued</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccruedIncomeTaxesCurrent" xlink:label="AccruedIncomeTaxesCurrent" xlink:title="AccruedIncomeTaxesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedIncomeTaxesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccruedIncomeTaxesCurrent_lbl" xml:lang="en-US" id="us-gaap_AccruedIncomeTaxesCurrent_lbl">Income taxes payable</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedIncomeTaxesCurrent" xlink:to="us-gaap_AccruedIncomeTaxesCurrent_lbl1" xlink:title="label: AccruedIncomeTaxesCurrent to us-gaap_AccruedIncomeTaxesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfStockLineItems" xlink:label="ClassOfStockLineItems" xlink:title="ClassOfStockLineItems" />
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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>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AccruedLiabilitiesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AccruedLiabilitiesCurrent_lbl" xml:lang="en-US" id="us-gaap_AccruedLiabilitiesCurrent_lbl">Accrued liabilities</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedLiabilitiesCurrent" xlink:to="us-gaap_AccruedLiabilitiesCurrent_lbl2" xlink:title="label: AccruedLiabilitiesCurrent to us-gaap_AccruedLiabilitiesCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="EmployeeRelatedLiabilitiesCurrent" xlink:title="EmployeeRelatedLiabilitiesCurrent" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherAccruedLiabilitiesCurrent" xlink:label="OtherAccruedLiabilitiesCurrent" xlink:title="OtherAccruedLiabilitiesCurrent" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AccruedLiabilitiesCurrentAbstract" xlink:label="AccruedLiabilitiesCurrentAbstract" xlink:title="AccruedLiabilitiesCurrentAbstract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:label="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:title="OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:label="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" xlink:title="AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinancialInstrumentAxis" xlink:label="FinancialInstrumentAxis" xlink:title="FinancialInstrumentAxis" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameAxis" xlink:label="PlanNameAxis" xlink:title="PlanNameAxis" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="IncomeStatementLocationAxis" xlink:title="IncomeStatementLocationAxis" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:label="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:title="NewAccountingPronouncementsPolicyPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl">Recently Issued Accounting Standards</link:label>
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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/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskCreditRisk" xlink:label="ConcentrationRiskCreditRisk" xlink:title="ConcentrationRiskCreditRisk" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets" xlink:label="DeferredTaxAssetsGoodwillAndIntangibleAssets" xlink:title="DeferredTaxAssetsGoodwillAndIntangibleAssets" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentRepurchasedFaceAmount" xlink:label="DebtInstrumentRepurchasedFaceAmount" xlink:title="DebtInstrumentRepurchasedFaceAmount" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife" xlink:label="PropertyPlantAndEquipmentUsefulLife" xlink:title="PropertyPlantAndEquipmentUsefulLife" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Exercisable, Weighted Average Remaining Contractual Term</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl">Period before options are exercisable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1 to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Award Requisite Service Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1 to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl">Vesting period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1 to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Award Vesting Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1 to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl">Weighted average period for recognition</link:label>
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1 to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl2" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl2">Share-Based Payment Arrangement, Nonvested Award, Cost Not yet Recognized, Period for Recognition</link:label>
    <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/2023/elts/us-gaap-2023.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl">Percentage of fair market value used to determine purchase price of stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Purchase Price of Common Stock, Percent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NumberOfOperatingSegments" xlink:label="NumberOfOperatingSegments" xlink:title="NumberOfOperatingSegments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NumberOfOperatingSegments_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NumberOfOperatingSegments_lbl" xml:lang="en-US" id="us-gaap_NumberOfOperatingSegments_lbl">Number of operating segments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfOperatingSegments" xlink:to="us-gaap_NumberOfOperatingSegments_lbl" xlink:title="label: NumberOfOperatingSegments to us-gaap_NumberOfOperatingSegments_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherCurrentAssetsMember" xlink:label="OtherCurrentAssetsMember" xlink:title="OtherCurrentAssetsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherCurrentAssetsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherCurrentAssetsMember_lbl" xml:lang="en-US" id="us-gaap_OtherCurrentAssetsMember_lbl">Other Current Assets [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCurrentAssetsMember" xlink:to="us-gaap_OtherCurrentAssetsMember_lbl" xlink:title="label: OtherCurrentAssetsMember to us-gaap_OtherCurrentAssetsMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember" xlink:label="SellingGeneralAndAdministrativeExpensesMember" xlink:title="SellingGeneralAndAdministrativeExpensesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl">Selling, General and Administrative [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpensesMember" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl" xlink:title="label: SellingGeneralAndAdministrativeExpensesMember to us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1">Selling, General and Administrative Expenses [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SellingGeneralAndAdministrativeExpensesMember" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" xlink:title="label: SellingGeneralAndAdministrativeExpensesMember to us-gaap_SellingGeneralAndAdministrativeExpensesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" xlink:label="ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" xlink:title="ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl">Gross Unrecognized Tax Benefits</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" xlink:to="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl" xlink:title="label: ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock to us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl1">Schedule of Unrecognized Tax Benefits Roll Forward [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock" xlink:to="us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl1" xlink:title="label: ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock to us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ConcentrationRiskPercentage1" xlink:label="ConcentrationRiskPercentage1" xlink:title="ConcentrationRiskPercentage1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConcentrationRiskPercentage1_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConcentrationRiskPercentage1_lbl" xml:lang="en-US" id="us-gaap_ConcentrationRiskPercentage1_lbl">Concentration percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConcentrationRiskPercentage1" xlink:to="us-gaap_ConcentrationRiskPercentage1_lbl" xlink:title="label: ConcentrationRiskPercentage1 to us-gaap_ConcentrationRiskPercentage1_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1" xlink:label="DebtInstrumentConvertibleConversionPrice1" xlink:title="DebtInstrumentConvertibleConversionPrice1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" xml:lang="en-US" id="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl">Conversion price per share (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPrice1" xlink:to="us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" xlink:title="label: DebtInstrumentConvertibleConversionPrice1 to us-gaap_DebtInstrumentConvertibleConversionPrice1_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="BalanceSheetLocationDomain" xlink:title="BalanceSheetLocationDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_BalanceSheetLocationDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_BalanceSheetLocationDomain_lbl" xml:lang="en-US" id="us-gaap_BalanceSheetLocationDomain_lbl">Balance Sheet Location [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BalanceSheetLocationDomain" xlink:to="us-gaap_BalanceSheetLocationDomain_lbl" xlink:title="label: BalanceSheetLocationDomain to us-gaap_BalanceSheetLocationDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CostOfSalesMember" xlink:label="CostOfSalesMember" xlink:title="CostOfSalesMember" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember_lbl" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesMember" xlink:to="us-gaap_CostOfSalesMember_lbl1" xlink:title="label: CostOfSalesMember to us-gaap_CostOfSalesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.xsd#us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" xlink:label="DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" xlink:title="DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl" xml:lang="en-US" id="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl">Employee contribution limit per calendar year</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" xlink:to="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl" xlink:title="label: DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount to us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl1" xml:lang="en-US" id="us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount_lbl1">Defined Contribution Plan, Maximum Annual Contributions Per Employee, Amount</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1">Other Noncurrent Liabilities [Table Text Block]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/label" xlink:title="us-gaap_RevenueFromContractWithCustomerAbstract_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerAbstract_lbl">Revenues [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/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1">Revenue:</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/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueFromContractWithCustomerTextBlock" xlink:label="RevenueFromContractWithCustomerTextBlock" xlink:title="RevenueFromContractWithCustomerTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl">Revenues</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTextBlock" xlink:to="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl" xlink:title="label: RevenueFromContractWithCustomerTextBlock to us-gaap_RevenueFromContractWithCustomerTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl1">Revenue from Contract with Customer [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTextBlock" xlink:to="us-gaap_RevenueFromContractWithCustomerTextBlock_lbl1" xlink:title="label: RevenueFromContractWithCustomerTextBlock to us-gaap_RevenueFromContractWithCustomerTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="OperatingLeaseRightOfUseAsset" xlink:title="OperatingLeaseRightOfUseAsset" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseRightOfUseAsset_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAsset_lbl">Right-of-use assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAsset" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset_lbl" xlink:title="label: OperatingLeaseRightOfUseAsset to us-gaap_OperatingLeaseRightOfUseAsset_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseRightOfUseAsset_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAsset_lbl1">Right-of-use operating lease assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAsset" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset_lbl1" xlink:title="label: OperatingLeaseRightOfUseAsset to us-gaap_OperatingLeaseRightOfUseAsset_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:label="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:title="OperatingLeaseLiabilitiesPaymentsDueAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl">Future Payments for Operating Lease Liabilities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl" xlink:title="label: OperatingLeaseLiabilitiesPaymentsDueAbstract to us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1">Lessee, Operating Lease, Liability, to be Paid, Fiscal Year Maturity [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilitiesPaymentsDueAbstract" xlink:to="us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" xlink:title="label: OperatingLeaseLiabilitiesPaymentsDueAbstract to us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeaseDescriptionTable" xlink:to="us-gaap_LesseeLeaseDescriptionTable_lbl" xlink:title="label: LesseeLeaseDescriptionTable to us-gaap_LesseeLeaseDescriptionTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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/2023/elts/us-gaap-2023.xsd#us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:label="EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" xlink:title="EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:label="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:title="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl2" xlink:title="label: CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents to us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeasePayments" xlink:label="OperatingLeasePayments" xlink:title="OperatingLeasePayments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeasePayments_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeasePayments_lbl" xml:lang="en-US" id="us-gaap_OperatingLeasePayments_lbl">Operating lease cash payments</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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeasePayments" xlink:to="us-gaap_OperatingLeasePayments_lbl1" xlink:title="label: OperatingLeasePayments to us-gaap_OperatingLeasePayments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:label="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" xlink:title="RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent" xlink:label="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:title="OperatingLeaseWeightedAverageDiscountRatePercent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl">Weighted average discount rate</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1">Operating Lease, Weighted Average Discount Rate, Percent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseWeightedAverageDiscountRatePercent" xlink:to="us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" xlink:title="label: OperatingLeaseWeightedAverageDiscountRatePercent to us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
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    <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>
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
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    <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/2023/elts/us-gaap-2023.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">2024</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/2023/elts/us-gaap-2023.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">2028</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/2023/elts/us-gaap-2023.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">2027</link:label>
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    <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/2023/elts/us-gaap-2023.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">2026</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/2023/elts/us-gaap-2023.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">2025</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/2023/elts/us-gaap-2023.xsd#us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock" xlink:label="LesseeOperatingLeaseLiabilityMaturityTableTextBlock" xlink:title="LesseeOperatingLeaseLiabilityMaturityTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock_lbl">Future Payments for Operating Lease Liabilities</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_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityMaturityTableTextBlock to us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock_lbl" />
    <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, to be Paid, 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/2023/elts/us-gaap-2023.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseExpense" xlink:to="us-gaap_OperatingLeaseExpense_lbl" xlink:title="label: OperatingLeaseExpense to us-gaap_OperatingLeaseExpense_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LessorOperatingLeasePaymentsToBeReceived" xlink:label="LessorOperatingLeasePaymentsToBeReceived" xlink:title="LessorOperatingLeasePaymentsToBeReceived" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl" xml:lang="en-US" id="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl">Lease payments to be received over term of sublease</link:label>
    <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, Payment to be Received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeasePaymentsToBeReceived" xlink:to="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl1" xlink:title="label: LessorOperatingLeasePaymentsToBeReceived to us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleAndLeasebackTransactionGainLossNet" xlink:label="SaleAndLeasebackTransactionGainLossNet" xlink:title="SaleAndLeasebackTransactionGainLossNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl" xml:lang="en-US" id="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl">Gain on sale of real estate assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SaleAndLeasebackTransactionGainLossNet" xlink:to="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl" xlink:title="label: SaleAndLeasebackTransactionGainLossNet to us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl1" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl1" xml:lang="en-US" id="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl1">Loss (gain) on sale of real estate assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SaleAndLeasebackTransactionGainLossNet" xlink:to="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl1" xlink:title="label: SaleAndLeasebackTransactionGainLossNet to us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl2" xml:lang="en-US" id="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl2">Sale and Leaseback Transaction, Gain (Loss), Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SaleAndLeasebackTransactionGainLossNet" xlink:to="us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl2" xlink:title="label: SaleAndLeasebackTransactionGainLossNet to us-gaap_SaleAndLeasebackTransactionGainLossNet_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseLiability" xlink:label="OperatingLeaseLiability" xlink:title="OperatingLeaseLiability" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiability_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_OperatingLeaseLiability_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseLiability_lbl">Operating lease liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiability" xlink:to="us-gaap_OperatingLeaseLiability_lbl" xlink:title="label: OperatingLeaseLiability to us-gaap_OperatingLeaseLiability_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiability" xlink:to="us-gaap_OperatingLeaseLiability_lbl1" xlink:title="label: OperatingLeaseLiability to us-gaap_OperatingLeaseLiability_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiability_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiability_lbl2" xml:lang="en-US" id="us-gaap_OperatingLeaseLiability_lbl2">Operating Lease, Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiability" xlink:to="us-gaap_OperatingLeaseLiability_lbl2" xlink:title="label: OperatingLeaseLiability to us-gaap_OperatingLeaseLiability_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="OperatingLeaseLiabilityCurrent" xlink:title="OperatingLeaseLiabilityCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_OperatingLeaseLiabilityCurrent_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityCurrent_lbl">Less: Current portion (included in other current liabilities)</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiabilityCurrent_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityCurrent_lbl1">Operating Lease, Liability, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilityCurrent" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent_lbl1" xlink:title="label: OperatingLeaseLiabilityCurrent to us-gaap_OperatingLeaseLiabilityCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
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    <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/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:label="OperatingLeaseLiabilityNoncurrent" xlink:title="OperatingLeaseLiabilityNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiabilityNoncurrent_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityNoncurrent_lbl">Long-term lease liabilities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiabilityNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityNoncurrent_lbl1">Total long-term lease liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilityNoncurrent" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent_lbl1" xlink:title="label: OperatingLeaseLiabilityNoncurrent to us-gaap_OperatingLeaseLiabilityNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList" xlink:to="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl" xlink:title="label: OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList to us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList" xlink:to="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl1" xlink:title="label: OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList to us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_LessorOperatingLeaseTermOfContract" xlink:label="LessorOperatingLeaseTermOfContract" xlink:title="LessorOperatingLeaseTermOfContract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtSecuritiesCurrentAbstract" xlink:label="DebtSecuritiesCurrentAbstract" xlink:title="DebtSecuritiesCurrentAbstract" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1">Share-Based Payment Arrangement, Employee [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementEmployeeMember" xlink:to="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xlink:title="label: ShareBasedPaymentArrangementEmployeeMember to us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:label="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:title="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl">Amortized cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostCurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1">Debt Securities, Available-for-Sale, Amortized Cost, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostCurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:label="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:title="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl">Amortized cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1">Debt Securities, Available-for-Sale, Amortized Cost, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:label="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:title="OperatingLeaseRightOfUseAssetAmortizationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl">Amortization of right-of-use operating lease assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:to="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl" xlink:title="label: OperatingLeaseRightOfUseAssetAmortizationExpense to us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1">Operating Lease, Right-of-Use Asset, Periodic Reduction</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:to="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xlink:title="label: OperatingLeaseRightOfUseAssetAmortizationExpense to us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquitySecuritiesFVNIAbstract" xlink:label="EquitySecuritiesFVNIAbstract" xlink:title="EquitySecuritiesFVNIAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFVNIAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesFVNIAbstract_lbl" xml:lang="en-US" id="us-gaap_EquitySecuritiesFVNIAbstract_lbl">Equity Securities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFVNIAbstract" xlink:to="us-gaap_EquitySecuritiesFVNIAbstract_lbl" xlink:title="label: EquitySecuritiesFVNIAbstract to us-gaap_EquitySecuritiesFVNIAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFVNIAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFVNIAbstract_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFVNIAbstract_lbl1">Equity Securities, FV-NI [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFVNIAbstract" xlink:to="us-gaap_EquitySecuritiesFVNIAbstract_lbl1" xlink:title="label: EquitySecuritiesFVNIAbstract to us-gaap_EquitySecuritiesFVNIAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration" xlink:label="ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration" xlink:title="ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration_lbl" xml:lang="en-US" id="us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration_lbl">Impairment, Long-Lived Asset, Held-for-Use, Statement of Income [Extensible Enumeration]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration" xlink:to="us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration_lbl" xlink:title="label: ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration to us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent" xlink:label="EffectiveIncomeTaxRateReconciliationFdiiPercent" xlink:title="EffectiveIncomeTaxRateReconciliationFdiiPercent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl">Foreign-derived intangible income benefit</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationFdiiPercent" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl" xlink:title="label: EffectiveIncomeTaxRateReconciliationFdiiPercent to us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl1" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl1">Effective Income Tax Rate Reconciliation, FDII, Percent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationFdiiPercent" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl1" xlink:title="label: EffectiveIncomeTaxRateReconciliationFdiiPercent to us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount" xlink:label="EffectiveIncomeTaxRateReconciliationFdiiAmount" xlink:title="EffectiveIncomeTaxRateReconciliationFdiiAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl">Foreign-derived intangible income benefit</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationFdiiAmount" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl" xlink:title="label: EffectiveIncomeTaxRateReconciliationFdiiAmount to us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl1" xml:lang="en-US" id="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl1">Effective Income Tax Rate Reconciliation, FDII, Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationFdiiAmount" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl1" xlink:title="label: EffectiveIncomeTaxRateReconciliationFdiiAmount to us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain" xlink:title="NameOfMajorCustomerDomain" />
    <link:label xlink:type="resource" xlink:label="srt_NameOfMajorCustomerDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_NameOfMajorCustomerDomain_lbl" xml:lang="en-US" id="srt_NameOfMajorCustomerDomain_lbl">Customer [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NameOfMajorCustomerDomain" xlink:to="srt_NameOfMajorCustomerDomain_lbl" xlink:title="label: NameOfMajorCustomerDomain to srt_NameOfMajorCustomerDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ExecutiveOfficerMember" xlink:label="ExecutiveOfficerMember" xlink:title="ExecutiveOfficerMember" />
    <link:label xlink:type="resource" xlink:label="srt_ExecutiveOfficerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="srt_ExecutiveOfficerMember_lbl" xml:lang="en-US" id="srt_ExecutiveOfficerMember_lbl">Executive Officers [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_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/2023/elts/srt-2023.xsd#srt_MajorCustomersAxis" xlink:label="MajorCustomersAxis" xlink:title="MajorCustomersAxis" />
    <link:label xlink:type="resource" xlink:label="srt_MajorCustomersAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MajorCustomersAxis_lbl" xml:lang="en-US" id="srt_MajorCustomersAxis_lbl">Customer [Axis]</link:label>
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
    <link:label xlink:type="resource" xlink:label="srt_RangeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeAxis_lbl" xml:lang="en-US" id="srt_RangeAxis_lbl">Statistical Measurement [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeAxis" xlink:to="srt_RangeAxis_lbl" xlink:title="label: RangeAxis to srt_RangeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RangeMember" xlink:to="srt_RangeMember_lbl" xlink:title="label: RangeMember to srt_RangeMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember" xlink:label="MaximumMember" xlink:title="MaximumMember" />
    <link:label xlink:type="resource" xlink:label="srt_MaximumMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_MaximumMember_lbl" xml:lang="en-US" id="srt_MaximumMember_lbl">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_lbl" xlink:title="label: MaximumMember to srt_MaximumMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MinimumMember" xlink:label="MinimumMember" xlink:title="MinimumMember" />
    <link:label xlink:type="resource" xlink:label="srt_MinimumMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" 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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock" xlink:label="ContractualObligationFiscalYearMaturityScheduleTableTextBlock" xlink:title="ContractualObligationFiscalYearMaturityScheduleTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl" xml:lang="en-US" id="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl">Debt Maturity Schedules</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligationFiscalYearMaturityScheduleTableTextBlock" xlink:to="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl" xlink:title="label: ContractualObligationFiscalYearMaturityScheduleTableTextBlock to srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl1" xml:lang="en-US" id="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl1">Contractual Obligation, Fiscal Year Maturity [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractualObligationFiscalYearMaturityScheduleTableTextBlock" xlink:to="srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl1" xlink:title="label: ContractualObligationFiscalYearMaturityScheduleTableTextBlock to srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ProductsAndServicesDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductsAndServicesDomain_lbl" xml:lang="en-US" id="srt_ProductsAndServicesDomain_lbl">Product and Service [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductsAndServicesDomain" xlink:to="srt_ProductsAndServicesDomain_lbl" xlink:title="label: ProductsAndServicesDomain to srt_ProductsAndServicesDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
    <link:label xlink:type="resource" xlink:label="srt_ProductOrServiceAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ProductOrServiceAxis_lbl" xml:lang="en-US" id="srt_ProductOrServiceAxis_lbl">Product and Service [Axis]</link:label>
    <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" />
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.xsd#dei_DocumentAnnualReport" xlink:label="DocumentAnnualReport" xlink:title="DocumentAnnualReport" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.xsd#dei_DocumentFinStmtErrorCorrectionFlag" xlink:label="DocumentFinStmtErrorCorrectionFlag" xlink:title="DocumentFinStmtErrorCorrectionFlag" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFinStmtErrorCorrectionFlag_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFinStmtErrorCorrectionFlag_lbl" xml:lang="en-US" id="dei_DocumentFinStmtErrorCorrectionFlag_lbl">Document Financial Statement Error Correction [Flag]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.xsd#dei_EntityInteractiveDataCurrent" xlink:label="EntityInteractiveDataCurrent" xlink:title="EntityInteractiveDataCurrent" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.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/2023/dei-2023.xsd#dei_IcfrAuditorAttestationFlag" xlink:label="IcfrAuditorAttestationFlag" xlink:title="IcfrAuditorAttestationFlag" />
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    <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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.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>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.xsd#dei_EntityRegistrantName" xlink:label="EntityRegistrantName" xlink:title="EntityRegistrantName" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.xsd#dei_EntityCentralIndexKey" xlink:label="EntityCentralIndexKey" xlink:title="EntityCentralIndexKey" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCentralIndexKey_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCentralIndexKey_lbl" xml:lang="en-US" id="dei_EntityCentralIndexKey_lbl">Entity Central Index Key</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.xsd#dei_EntityFileNumber" xlink:label="EntityFileNumber" xlink:title="EntityFileNumber" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.xsd#dei_EntityTaxIdentificationNumber" xlink:label="EntityTaxIdentificationNumber" xlink:title="EntityTaxIdentificationNumber" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.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/2023/dei-2023.xsd#dei_EntityWellKnownSeasonedIssuer" xlink:label="EntityWellKnownSeasonedIssuer" xlink:title="EntityWellKnownSeasonedIssuer" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.xsd#dei_EntityShellCompany" xlink:label="EntityShellCompany" xlink:title="EntityShellCompany" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.xsd#dei_EntityAddressCityOrTown" xlink:label="EntityAddressCityOrTown" xlink:title="EntityAddressCityOrTown" />
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    <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/2023/dei-2023.xsd#dei_EntityAddressCountry" xlink:label="EntityAddressCountry" xlink:title="EntityAddressCountry" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressCountry_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressCountry_lbl" xml:lang="en-US" id="dei_EntityAddressCountry_lbl">Entity Address, Country</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressCountry" xlink:to="dei_EntityAddressCountry_lbl" xlink:title="label: EntityAddressCountry to dei_EntityAddressCountry_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.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/2023/dei-2023.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/2023/dei-2023.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/2023/dei-2023.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/2023/dei-2023.xsd#dei_NoTradingSymbolFlag" xlink:label="NoTradingSymbolFlag" xlink:title="NoTradingSymbolFlag" />
    <link:label xlink:type="resource" xlink:label="dei_NoTradingSymbolFlag_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_NoTradingSymbolFlag_lbl" xml:lang="en-US" id="dei_NoTradingSymbolFlag_lbl">No Trading Symbol Flag</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NoTradingSymbolFlag" xlink:to="dei_NoTradingSymbolFlag_lbl" xlink:title="label: NoTradingSymbolFlag to dei_NoTradingSymbolFlag_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2023/dei-2023.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/2023/dei-2023.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/2023/dei-2023.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/2023/dei-2023.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/2023/dei-2023.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/2023/dei-2023.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-20231231.xsd#ions_CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:label="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:title="CollaborativeArrangementsAndLicensingAgreementsAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1">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="CollaborativeArrangementsAndLicensingAgreementsAbstract" xlink:to="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" xlink:title="label: CollaborativeArrangementsAndLicensingAgreementsAbstract to ions_CollaborativeArrangementsAndLicensingAgreementsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_ConvertibleSeniorNotes175PercentMember" xlink:label="ConvertibleSeniorNotes175PercentMember" xlink:title="ConvertibleSeniorNotes175PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes175PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentMember_lbl">1.75 percent convertible senior notes due June 2028.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes175PercentMember" xlink:to="ions_ConvertibleSeniorNotes175PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes175PercentMember to ions_ConvertibleSeniorNotes175PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes175PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentMember_lbl1">Convertible Senior Notes 1.75 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes175PercentMember" xlink:to="ions_ConvertibleSeniorNotes175PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes175PercentMember to ions_ConvertibleSeniorNotes175PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes175PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentMember_lbl2">1.75% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes175PercentMember" xlink:to="ions_ConvertibleSeniorNotes175PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes175PercentMember to ions_ConvertibleSeniorNotes175PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes175PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes175PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes175PercentMember_lbl3">1.75 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes175PercentMember" xlink:to="ions_ConvertibleSeniorNotes175PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes175PercentMember to ions_ConvertibleSeniorNotes175PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_LongTermObligationsCurrent" xlink:label="LongTermObligationsCurrent" xlink:title="LongTermObligationsCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermObligationsCurrent_lbl" xml:lang="en-US" id="ions_LongTermObligationsCurrent_lbl">Amount of long-term debt, lease obligations and other obligations., classified as current.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsCurrent" xlink:to="ions_LongTermObligationsCurrent_lbl" xlink:title="label: LongTermObligationsCurrent to ions_LongTermObligationsCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligationsCurrent_lbl1" xml:lang="en-US" id="ions_LongTermObligationsCurrent_lbl1">Long-term Obligations, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsCurrent" xlink:to="ions_LongTermObligationsCurrent_lbl1" xlink:title="label: LongTermObligationsCurrent to ions_LongTermObligationsCurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsCurrent_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_LongTermObligationsCurrent_lbl2" xml:lang="en-US" id="ions_LongTermObligationsCurrent_lbl2">Less: current portion</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsCurrent" xlink:to="ions_LongTermObligationsCurrent_lbl2" xlink:title="label: LongTermObligationsCurrent to ions_LongTermObligationsCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_LongTermObligationsNoncurrent" xlink:label="LongTermObligationsNoncurrent" xlink:title="LongTermObligationsNoncurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermObligationsNoncurrent_lbl" xml:lang="en-US" id="ions_LongTermObligationsNoncurrent_lbl">Amount of long-term debt, lease obligations and other obligations, classified as noncurrent.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsNoncurrent" xlink:to="ions_LongTermObligationsNoncurrent_lbl" xlink:title="label: LongTermObligationsNoncurrent to ions_LongTermObligationsNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligationsNoncurrent_lbl1" xml:lang="en-US" id="ions_LongTermObligationsNoncurrent_lbl1">Long-term Obligations, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsNoncurrent" xlink:to="ions_LongTermObligationsNoncurrent_lbl1" xlink:title="label: LongTermObligationsNoncurrent to ions_LongTermObligationsNoncurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligationsNoncurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LongTermObligationsNoncurrent_lbl2" xml:lang="en-US" id="ions_LongTermObligationsNoncurrent_lbl2">Total Long-Term Obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligationsNoncurrent" xlink:to="ions_LongTermObligationsNoncurrent_lbl2" xlink:title="label: LongTermObligationsNoncurrent to ions_LongTermObligationsNoncurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:label="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:title="LiabilityRelatedToSaleOfFutureRoyaltiesNet" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl">Amount, after accumulated amortization, of the unamortized liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate method.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNet to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl1" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl1">Liability Related to Sale of Future Royalties, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl1" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNet to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl2" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl2">Liability related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl2" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNet to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl3" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl3" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl3">Net liability related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl3" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNet to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl3" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl4" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl4" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl4">Liability related to sale of future royalties, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNet" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl4" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNet to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet_lbl4" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligations" xlink:to="ions_LongTermObligations_lbl" xlink:title="label: LongTermObligations to ions_LongTermObligations_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligations_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermObligations_lbl1" xml:lang="en-US" id="ions_LongTermObligations_lbl1">Long-term Obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligations" xlink:to="ions_LongTermObligations_lbl1" xlink:title="label: LongTermObligations to ions_LongTermObligations_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligations_lbl2" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="ions_LongTermObligations_lbl2" xml:lang="en-US" id="ions_LongTermObligations_lbl2">Total</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermObligations" xlink:to="ions_LongTermObligations_lbl2" xlink:title="label: LongTermObligations to ions_LongTermObligations_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl2">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_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/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl3">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_lbl3" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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/terseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl2">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_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/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl3">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_lbl3" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_SupplementalFinancialDataAbstract" xlink:label="SupplementalFinancialDataAbstract" xlink:title="SupplementalFinancialDataAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_SupplementalFinancialDataAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SupplementalFinancialDataAbstract_lbl1" xml:lang="en-US" id="ions_SupplementalFinancialDataAbstract_lbl1">Supplemental Financial Data [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SupplementalFinancialDataAbstract" xlink:to="ions_SupplementalFinancialDataAbstract_lbl1" xlink:title="label: SupplementalFinancialDataAbstract to ions_SupplementalFinancialDataAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:label="NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:title="NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl" xml:lang="en-US" id="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl">Number of lots of undeveloped land adjacent to the Company's headquarters transferred to real estate investor.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:to="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl" xlink:title="label: NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor to ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl1" xml:lang="en-US" id="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl1">Number of lots of undeveloped land transferred to real estate investor</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:to="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl1" xlink:title="label: NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor to ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl2" xml:lang="en-US" id="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl2">Number of lots of undeveloped land transferred to real estate investor</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor" xlink:to="ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl2" xlink:title="label: NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor to ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_CarlsbadOfficeSpaceMember" xlink:label="CarlsbadOfficeSpaceMember" xlink:title="CarlsbadOfficeSpaceMember" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpaceMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CarlsbadOfficeSpaceMember_lbl" xml:lang="en-US" id="ions_CarlsbadOfficeSpaceMember_lbl">Additional office space 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="CarlsbadOfficeSpaceMember" xlink:to="ions_CarlsbadOfficeSpaceMember_lbl" xlink:title="label: CarlsbadOfficeSpaceMember to ions_CarlsbadOfficeSpaceMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpaceMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CarlsbadOfficeSpaceMember_lbl1" xml:lang="en-US" id="ions_CarlsbadOfficeSpaceMember_lbl1">Carlsbad Office Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadOfficeSpaceMember" xlink:to="ions_CarlsbadOfficeSpaceMember_lbl1" xlink:title="label: CarlsbadOfficeSpaceMember to ions_CarlsbadOfficeSpaceMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpaceMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CarlsbadOfficeSpaceMember_lbl2" xml:lang="en-US" id="ions_CarlsbadOfficeSpaceMember_lbl2">Carlsbad Office Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadOfficeSpaceMember" xlink:to="ions_CarlsbadOfficeSpaceMember_lbl2" xlink:title="label: CarlsbadOfficeSpaceMember to ions_CarlsbadOfficeSpaceMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.xsd#ions_CarlsbadWarehouseSpaceMember" xlink:label="CarlsbadWarehouseSpaceMember" xlink:title="CarlsbadWarehouseSpaceMember" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadWarehouseSpaceMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CarlsbadWarehouseSpaceMember_lbl" xml:lang="en-US" id="ions_CarlsbadWarehouseSpaceMember_lbl">Warehouse space 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="CarlsbadWarehouseSpaceMember" xlink:to="ions_CarlsbadWarehouseSpaceMember_lbl" xlink:title="label: CarlsbadWarehouseSpaceMember to ions_CarlsbadWarehouseSpaceMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadWarehouseSpaceMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CarlsbadWarehouseSpaceMember_lbl1" xml:lang="en-US" id="ions_CarlsbadWarehouseSpaceMember_lbl1">Carlsbad Warehouse Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadWarehouseSpaceMember" xlink:to="ions_CarlsbadWarehouseSpaceMember_lbl1" xlink:title="label: CarlsbadWarehouseSpaceMember to ions_CarlsbadWarehouseSpaceMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadWarehouseSpaceMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CarlsbadWarehouseSpaceMember_lbl2" xml:lang="en-US" id="ions_CarlsbadWarehouseSpaceMember_lbl2">Carlsbad Warehouse Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadWarehouseSpaceMember" xlink:to="ions_CarlsbadWarehouseSpaceMember_lbl2" xlink:title="label: CarlsbadWarehouseSpaceMember to ions_CarlsbadWarehouseSpaceMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:label="LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:title="LessorOperatingLeaseNumberOfOptionsToExtendLease" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl" xml:lang="en-US" id="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl">The number of options to extend the lease under the lessor's operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl" xlink:title="label: LessorOperatingLeaseNumberOfOptionsToExtendLease to ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xml:lang="en-US" id="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl1">Lessor, 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="LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xlink:title="label: LessorOperatingLeaseNumberOfOptionsToExtendLease to ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl2" xml:lang="en-US" id="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl2">Number of options to extend sublease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl2" xlink:title="label: LessorOperatingLeaseNumberOfOptionsToExtendLease to ions_LessorOperatingLeaseNumberOfOptionsToExtendLease_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember" xlink:label="ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember" xlink:title="ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl">Portion of total proceeds from the issuance of 0 percent convertible senior notes due April 2026 used to pay the remaining principal balance of the 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="ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember" xlink:to="ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl" xlink:title="label: ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember to ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember_lbl1">Convertible Senior Notes 0 Percent, Used to Pay Remaining Balance of 1 Percent Convertible Senior Notes [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember" xlink:label="ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember" xlink:title="ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember" />
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    <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>
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.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:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_CallSpread" xlink:label="CallSpread" xlink:title="CallSpread" />
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:label="InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:title="InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" />
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    <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-20231231.xsd#ions_WainuaJointDevelopmentRevenueMember" xlink:label="WainuaJointDevelopmentRevenueMember" xlink:title="WainuaJointDevelopmentRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_WainuaJointDevelopmentRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_WainuaJointDevelopmentRevenueMember_lbl" xml:lang="en-US" id="ions_WainuaJointDevelopmentRevenueMember_lbl">Joint development revenue for WAINUA (eplontersen).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainuaJointDevelopmentRevenueMember" xlink:to="ions_WainuaJointDevelopmentRevenueMember_lbl" xlink:title="label: WainuaJointDevelopmentRevenueMember to ions_WainuaJointDevelopmentRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_WainuaJointDevelopmentRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_WainuaJointDevelopmentRevenueMember_lbl1" xml:lang="en-US" id="ions_WainuaJointDevelopmentRevenueMember_lbl1">WAINUA Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainuaJointDevelopmentRevenueMember" xlink:to="ions_WainuaJointDevelopmentRevenueMember_lbl1" xlink:title="label: WainuaJointDevelopmentRevenueMember to ions_WainuaJointDevelopmentRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_WainuaJointDevelopmentRevenueMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_WainuaJointDevelopmentRevenueMember_lbl2" xml:lang="en-US" id="ions_WainuaJointDevelopmentRevenueMember_lbl2">WAINUA Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WainuaJointDevelopmentRevenueMember" xlink:to="ions_WainuaJointDevelopmentRevenueMember_lbl2" xlink:title="label: WainuaJointDevelopmentRevenueMember to ions_WainuaJointDevelopmentRevenueMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_OtherCommercialMember" xlink:label="OtherCommercialMember" xlink:title="OtherCommercialMember" />
    <link:label xlink:type="resource" xlink:label="ions_OtherCommercialMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtherCommercialMember_lbl" xml:lang="en-US" id="ions_OtherCommercialMember_lbl">Revenue from the sale of other medicines commercially as well as licensing and royalty revenue from other medicines, including TEGSEDI and WAYLIVRA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCommercialMember" xlink:to="ions_OtherCommercialMember_lbl" xlink:title="label: OtherCommercialMember to ions_OtherCommercialMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtherCommercialMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtherCommercialMember_lbl1" xml:lang="en-US" id="ions_OtherCommercialMember_lbl1">Other Commercial [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCommercialMember" xlink:to="ions_OtherCommercialMember_lbl1" xlink:title="label: OtherCommercialMember to ions_OtherCommercialMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OtherCommercialMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OtherCommercialMember_lbl2" xml:lang="en-US" id="ions_OtherCommercialMember_lbl2">Other Commercial Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCommercialMember" xlink:to="ions_OtherCommercialMember_lbl2" xlink:title="label: OtherCommercialMember to ions_OtherCommercialMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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>
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_DeferredTaxAssetsLeasingArrangements" xlink:label="DeferredTaxAssetsLeasingArrangements" xlink:title="DeferredTaxAssetsLeasingArrangements" />
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseLossOnDebtTransactionsAmount" xlink:label="EffectiveIncomeTaxRateReconciliationNondeductibleExpenseLossOnDebtTransactionsAmount" xlink:title="EffectiveIncomeTaxRateReconciliationNondeductibleExpenseLossOnDebtTransactionsAmount" />
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_OperatingLossCarryforwardsUtilized" xlink:label="OperatingLossCarryforwardsUtilized" xlink:title="OperatingLossCarryforwardsUtilized" />
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_RoyaltyRevenueMonetizationAbstract" xlink:label="RoyaltyRevenueMonetizationAbstract" xlink:title="RoyaltyRevenueMonetizationAbstract" />
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:label="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:title="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl" xml:lang="en-US" id="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl">The maximum amount of annual sales on which royalty payments are paid under the royalty purchase agreement.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1">Maximum amount of annual sales on which royalty payments are paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:to="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" xlink:title="label: MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid to ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl2">Maximum amount of annual sales on which royalty payments are paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:to="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl2" xlink:title="label: MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid to ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaMember" xlink:to="ions_SpinrazaMember_lbl" xlink:title="label: SpinrazaMember to ions_SpinrazaMember_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaMember" xlink:to="ions_SpinrazaMember_lbl1" xlink:title="label: SpinrazaMember to ions_SpinrazaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SpinrazaMember_lbl2" xml:lang="en-US" id="ions_SpinrazaMember_lbl2">SPINRAZA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaMember" xlink:to="ions_SpinrazaMember_lbl2" xlink:title="label: SpinrazaMember to ions_SpinrazaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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>
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.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>
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    <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-20231231.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-20231231.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-20231231.xsd#ions_RoyaltyPurchaseAgreementMember" xlink:label="RoyaltyPurchaseAgreementMember" xlink:title="RoyaltyPurchaseAgreementMember" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPurchaseAgreementMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPurchaseAgreementMember_lbl" xml:lang="en-US" id="ions_RoyaltyPurchaseAgreementMember_lbl">In January 2023, the Company entered into a royalty purchase agreement with Royalty Pharma to monetize a portion of future SPINRAZA and pelacarsen royalties the Company is entitled to under arrangements with Biogen and Novartis, respectively.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPurchaseAgreementMember" xlink:to="ions_RoyaltyPurchaseAgreementMember_lbl" xlink:title="label: RoyaltyPurchaseAgreementMember to ions_RoyaltyPurchaseAgreementMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPurchaseAgreementMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPurchaseAgreementMember_lbl1" xml:lang="en-US" id="ions_RoyaltyPurchaseAgreementMember_lbl1">Royalty Purchase Agreement [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPurchaseAgreementMember" xlink:to="ions_RoyaltyPurchaseAgreementMember_lbl1" xlink:title="label: RoyaltyPurchaseAgreementMember to ions_RoyaltyPurchaseAgreementMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPurchaseAgreementMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPurchaseAgreementMember_lbl2" xml:lang="en-US" id="ions_RoyaltyPurchaseAgreementMember_lbl2">Royalty Purchase Agreement [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPurchaseAgreementMember" xlink:to="ions_RoyaltyPurchaseAgreementMember_lbl2" xlink:title="label: RoyaltyPurchaseAgreementMember to ions_RoyaltyPurchaseAgreementMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:label="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:title="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl">The cash outflow paid to third parties for transaction costs in connection with a monetization transaction of future SPINRAZA and pelacarsen royalties the Company is entitled to under collaboration and licensing agreements.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl1" xml:lang="en-US" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl1">Payments for Transaction Costs Related to Sale of Future Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl1" xlink:title="label: PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties to ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl2" xml:lang="en-US" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl2">Payments of transaction costs related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl2" xlink:title="label: PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties to ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl3" xml:lang="en-US" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl3">Transaction costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl3" xlink:title="label: PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties to ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl3" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl4" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl4" xml:lang="en-US" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl4">Issuance costs related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl4" xlink:title="label: PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties to ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties_lbl4" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:label="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:title="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl">Amount of amortization expense attributable to the sale of future royalties.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" xml:lang="en-US" id="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1">Amortization of Issuance Costs Related to Sale of Future Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" xlink:title="label: AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties to ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl2" xml:lang="en-US" id="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl2">Amortization of issuance costs related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" xlink:to="ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl2" xlink:title="label: AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties to ions_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_ProceedsFromSaleOfFutureRoyalties" xlink:label="ProceedsFromSaleOfFutureRoyalties" xlink:title="ProceedsFromSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ProceedsFromSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_ProceedsFromSaleOfFutureRoyalties_lbl">The cash inflow from the sale of future royalties under a royalty purchase agreement.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfFutureRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ProceedsFromSaleOfFutureRoyalties_lbl1" xml:lang="en-US" id="ions_ProceedsFromSaleOfFutureRoyalties_lbl1">Proceeds from Sale of Future Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfFutureRoyalties" xlink:to="ions_ProceedsFromSaleOfFutureRoyalties_lbl1" xlink:title="label: ProceedsFromSaleOfFutureRoyalties to ions_ProceedsFromSaleOfFutureRoyalties_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfFutureRoyalties_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ProceedsFromSaleOfFutureRoyalties_lbl2" xml:lang="en-US" id="ions_ProceedsFromSaleOfFutureRoyalties_lbl2">Proceeds from sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfFutureRoyalties" xlink:to="ions_ProceedsFromSaleOfFutureRoyalties_lbl2" xlink:title="label: ProceedsFromSaleOfFutureRoyalties to ions_ProceedsFromSaleOfFutureRoyalties_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_RoyaltyPayments" xlink:label="RoyaltyPayments" xlink:title="RoyaltyPayments" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPayments_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPayments_lbl" xml:lang="en-US" id="ions_RoyaltyPayments_lbl">The amount of royalty payments made during the period under a royalty purchase agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPayments" xlink:to="ions_RoyaltyPayments_lbl" xlink:title="label: RoyaltyPayments to ions_RoyaltyPayments_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPayments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPayments_lbl1" xml:lang="en-US" id="ions_RoyaltyPayments_lbl1">Royalty Payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPayments" xlink:to="ions_RoyaltyPayments_lbl1" xlink:title="label: RoyaltyPayments to ions_RoyaltyPayments_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPayments_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="ions_RoyaltyPayments_lbl2" xml:lang="en-US" id="ions_RoyaltyPayments_lbl2">Non-cash royalty revenue related to sale of royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPayments" xlink:to="ions_RoyaltyPayments_lbl2" xlink:title="label: RoyaltyPayments to ions_RoyaltyPayments_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPayments_lbl3" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_RoyaltyPayments_lbl3" xml:lang="en-US" id="ions_RoyaltyPayments_lbl3">Royalty payments to Royalty Pharma</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPayments" xlink:to="ions_RoyaltyPayments_lbl3" xlink:title="label: RoyaltyPayments to ions_RoyaltyPayments_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:label="InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:title="InterestExpenseRelatedToSaleOfFutureRoyalties" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl" xml:lang="en-US" id="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl">Amount of interest expense using the effective interest rate method related to the sale of future royalties.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:to="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl" xlink:title="label: InterestExpenseRelatedToSaleOfFutureRoyalties to ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl1" xml:lang="en-US" id="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl1">Interest Expense Related to Sale of Future Royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:to="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl1" xlink:title="label: InterestExpenseRelatedToSaleOfFutureRoyalties to ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl2" xml:lang="en-US" id="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl2">Non-cash interest related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:to="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl2" xlink:title="label: InterestExpenseRelatedToSaleOfFutureRoyalties to ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl3" xml:lang="en-US" id="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl3">Interest expense related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpenseRelatedToSaleOfFutureRoyalties" xlink:to="ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl3" xlink:title="label: InterestExpenseRelatedToSaleOfFutureRoyalties to ions_InterestExpenseRelatedToSaleOfFutureRoyalties_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross" xlink:label="LiabilityRelatedToSaleOfFutureRoyaltiesGross" xlink:title="LiabilityRelatedToSaleOfFutureRoyaltiesGross" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl">Amount, before accumulated amortization, of the liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate method.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesGross" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesGross to ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl1" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl1">Liability Related to Sale of Future Royalties, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesGross" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl1" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesGross to ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl2" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl2">Liability related to sale of future royalties</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesGross" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl2" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesGross to ions_LiabilityRelatedToSaleOfFutureRoyaltiesGross_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_MeasurementPeriodForAlternativePayoutMechanism" xlink:label="MeasurementPeriodForAlternativePayoutMechanism" xlink:title="MeasurementPeriodForAlternativePayoutMechanism" />
    <link:label xlink:type="resource" xlink:label="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl" xml:lang="en-US" id="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl">Measurement period for alternative payout mechanism, or the Alternative Calculation, included in equity-based award, 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="MeasurementPeriodForAlternativePayoutMechanism" xlink:to="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl" xlink:title="label: MeasurementPeriodForAlternativePayoutMechanism to ions_MeasurementPeriodForAlternativePayoutMechanism_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl1" xml:lang="en-US" id="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl1">Measurement Period for Alternative Payout Mechanism</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MeasurementPeriodForAlternativePayoutMechanism" xlink:to="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl1" xlink:title="label: MeasurementPeriodForAlternativePayoutMechanism to ions_MeasurementPeriodForAlternativePayoutMechanism_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl2" xml:lang="en-US" id="ions_MeasurementPeriodForAlternativePayoutMechanism_lbl2">Measurement period for Alternative Calculation</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_TermOfAlternativePayoutMechanism" xlink:label="TermOfAlternativePayoutMechanism" xlink:title="TermOfAlternativePayoutMechanism" />
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    <link:label xlink:type="resource" xlink:label="ions_Granted2020Through2022Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Granted2020Through2022Member_lbl2" xml:lang="en-US" id="ions_Granted2020Through2022Member_lbl2">Granted 2020 through 2022 [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_GrantedIn2023Member" xlink:label="GrantedIn2023Member" xlink:title="GrantedIn2023Member" />
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    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2023Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GrantedIn2023Member_lbl2" xml:lang="en-US" id="ions_GrantedIn2023Member_lbl2">Granted in 2023 [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.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>
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl2" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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>
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    <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-20231231.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-20231231.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-20231231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:to="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl" xlink:title="label: PeriodToMakeInterestOnlyPaymentsOnMortgageLoan to ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:to="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl1" xlink:title="label: PeriodToMakeInterestOnlyPaymentsOnMortgageLoan to ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl2" xml:lang="en-US" id="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl2">Period to make interest only payments on mortgage loan</link:label>
    <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-20231231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingFacilityMortgageMember" xlink:to="ions_ManufacturingFacilityMortgageMember_lbl" xlink:title="label: ManufacturingFacilityMortgageMember to ions_ManufacturingFacilityMortgageMember_lbl" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingFacilityMortgageMember" xlink:to="ions_ManufacturingFacilityMortgageMember_lbl2" xlink:title="label: ManufacturingFacilityMortgageMember to ions_ManufacturingFacilityMortgageMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:label="NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:title="NewResearchAndDevelopmentFacilityInCarlsbadCAMember" />
    <link:label xlink:type="resource" xlink:label="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl" xml:lang="en-US" id="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl">New research and development (R&amp;D) facility in Carlsbad, California composed of R&amp;D and office space.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:to="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl" xlink:title="label: NewResearchAndDevelopmentFacilityInCarlsbadCAMember to ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl1" xml:lang="en-US" id="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl1">New Research and Development Facility in Carlsbad, CA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:to="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl1" xlink:title="label: NewResearchAndDevelopmentFacilityInCarlsbadCAMember to ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl2" xml:lang="en-US" id="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl2">New R&amp;D Facility in Carlsbad, CA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewResearchAndDevelopmentFacilityInCarlsbadCAMember" xlink:to="ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl2" xlink:title="label: NewResearchAndDevelopmentFacilityInCarlsbadCAMember to ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_EarlyRepaymentOfConvertibleDebt" xlink:label="EarlyRepaymentOfConvertibleDebt" xlink:title="EarlyRepaymentOfConvertibleDebt" />
    <link:label xlink:type="resource" xlink:label="ions_EarlyRepaymentOfConvertibleDebt_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EarlyRepaymentOfConvertibleDebt_lbl" xml:lang="en-US" id="ions_EarlyRepaymentOfConvertibleDebt_lbl">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.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EarlyRepaymentOfConvertibleDebt" xlink:to="ions_EarlyRepaymentOfConvertibleDebt_lbl" xlink:title="label: EarlyRepaymentOfConvertibleDebt to ions_EarlyRepaymentOfConvertibleDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EarlyRepaymentOfConvertibleDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EarlyRepaymentOfConvertibleDebt_lbl1" xml:lang="en-US" id="ions_EarlyRepaymentOfConvertibleDebt_lbl1">Early Repayment of Convertible Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EarlyRepaymentOfConvertibleDebt" xlink:to="ions_EarlyRepaymentOfConvertibleDebt_lbl1" xlink:title="label: EarlyRepaymentOfConvertibleDebt to ions_EarlyRepaymentOfConvertibleDebt_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EarlyRepaymentOfConvertibleDebt_lbl2" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_EarlyRepaymentOfConvertibleDebt_lbl2" xml:lang="en-US" id="ions_EarlyRepaymentOfConvertibleDebt_lbl2">Repurchase of convertible senior notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EarlyRepaymentOfConvertibleDebt" xlink:to="ions_EarlyRepaymentOfConvertibleDebt_lbl2" xlink:title="label: EarlyRepaymentOfConvertibleDebt to ions_EarlyRepaymentOfConvertibleDebt_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_ProceedsFromRealEstateTransaction" xlink:label="ProceedsFromRealEstateTransaction" xlink:title="ProceedsFromRealEstateTransaction" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromRealEstateTransaction_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ProceedsFromRealEstateTransaction_lbl" xml:lang="en-US" id="ions_ProceedsFromRealEstateTransaction_lbl">The cash inflow from the transfer of legal ownership of two lots of undeveloped land to a real estate investor.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromRealEstateTransaction" xlink:to="ions_ProceedsFromRealEstateTransaction_lbl" xlink:title="label: ProceedsFromRealEstateTransaction to ions_ProceedsFromRealEstateTransaction_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromRealEstateTransaction_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ProceedsFromRealEstateTransaction_lbl1" xml:lang="en-US" id="ions_ProceedsFromRealEstateTransaction_lbl1">Proceeds from Real Estate Transaction</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromRealEstateTransaction" xlink:to="ions_ProceedsFromRealEstateTransaction_lbl1" xlink:title="label: ProceedsFromRealEstateTransaction to ions_ProceedsFromRealEstateTransaction_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromRealEstateTransaction_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ProceedsFromRealEstateTransaction_lbl2" xml:lang="en-US" id="ions_ProceedsFromRealEstateTransaction_lbl2">Proceeds from real estate transaction</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromRealEstateTransaction" xlink:to="ions_ProceedsFromRealEstateTransaction_lbl2" xlink:title="label: ProceedsFromRealEstateTransaction to ions_ProceedsFromRealEstateTransaction_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_NonCashCapitalAndPatentExpenditures" xlink:label="NonCashCapitalAndPatentExpenditures" xlink:title="NonCashCapitalAndPatentExpenditures" />
    <link:label xlink:type="resource" xlink:label="ions_NonCashCapitalAndPatentExpenditures_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NonCashCapitalAndPatentExpenditures_lbl" xml:lang="en-US" id="ions_NonCashCapitalAndPatentExpenditures_lbl">Future cash outflow to pay for purchases of fixed assets and patents that have been incurred.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonCashCapitalAndPatentExpenditures" xlink:to="ions_NonCashCapitalAndPatentExpenditures_lbl" xlink:title="label: NonCashCapitalAndPatentExpenditures to ions_NonCashCapitalAndPatentExpenditures_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NonCashCapitalAndPatentExpenditures_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NonCashCapitalAndPatentExpenditures_lbl1" xml:lang="en-US" id="ions_NonCashCapitalAndPatentExpenditures_lbl1">Non-cash Capital and Patent Expenditures</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonCashCapitalAndPatentExpenditures" xlink:to="ions_NonCashCapitalAndPatentExpenditures_lbl1" xlink:title="label: NonCashCapitalAndPatentExpenditures to ions_NonCashCapitalAndPatentExpenditures_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NonCashCapitalAndPatentExpenditures_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NonCashCapitalAndPatentExpenditures_lbl2" xml:lang="en-US" id="ions_NonCashCapitalAndPatentExpenditures_lbl2">Amounts accrued for capital and patent expenditures</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonCashCapitalAndPatentExpenditures" xlink:to="ions_NonCashCapitalAndPatentExpenditures_lbl2" xlink:title="label: NonCashCapitalAndPatentExpenditures to ions_NonCashCapitalAndPatentExpenditures_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized" xlink:label="NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized" xlink:title="NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized" />
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_PaymentToLicenseTechnology" xlink:label="PaymentToLicenseTechnology" xlink:title="PaymentToLicenseTechnology" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentToLicenseTechnology" xlink:to="ions_PaymentToLicenseTechnology_lbl2" xlink:title="label: PaymentToLicenseTechnology to ions_PaymentToLicenseTechnology_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_MetagenomiLicenseAgreementMember" xlink:label="MetagenomiLicenseAgreementMember" xlink:title="MetagenomiLicenseAgreementMember" />
    <link:label xlink:type="resource" xlink:label="ions_MetagenomiLicenseAgreementMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MetagenomiLicenseAgreementMember_lbl" xml:lang="en-US" id="ions_MetagenomiLicenseAgreementMember_lbl">License 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="MetagenomiLicenseAgreementMember" xlink:to="ions_MetagenomiLicenseAgreementMember_lbl" xlink:title="label: MetagenomiLicenseAgreementMember to ions_MetagenomiLicenseAgreementMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MetagenomiLicenseAgreementMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MetagenomiLicenseAgreementMember_lbl1" xml:lang="en-US" id="ions_MetagenomiLicenseAgreementMember_lbl1">Metagenomi License Agreement [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MetagenomiLicenseAgreementMember" xlink:to="ions_MetagenomiLicenseAgreementMember_lbl1" xlink:title="label: MetagenomiLicenseAgreementMember to ions_MetagenomiLicenseAgreementMember_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock" xlink:label="LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock" xlink:title="LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock" />
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    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock_lbl1" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock_lbl1">Liability Related to Sale of Future Royalties, 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="LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock_lbl2" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock to ions_LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_AccruedLiabilitiesPolicyPolicyTextBlock" xlink:label="AccruedLiabilitiesPolicyPolicyTextBlock" xlink:title="AccruedLiabilitiesPolicyPolicyTextBlock" />
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_ResearchDevelopmentAndPatentMember" xlink:label="ResearchDevelopmentAndPatentMember" xlink:title="ResearchDevelopmentAndPatentMember" />
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:label="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:label="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
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    <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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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>
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    <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>
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    <link:loc xlink:type="locator" xlink:href="ions-20231231.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>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" xlink:to="ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent_lbl2" xlink:title="label: DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent to ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" xlink:label="EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" xlink:title="EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl" xml:lang="en-US" id="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl">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).</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" xlink:to="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl2" xlink:title="label: EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain to ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:label="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:title="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" />
    <link:label xlink:type="resource" xlink:label="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl" xml:lang="en-US" id="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl">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).</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:to="ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl2" xlink:title="label: EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss to ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange2" xlink:to="ions_MaximumContractMaturityPeriodRange2_lbl" xlink:title="label: MaximumContractMaturityPeriodRange2 to ions_MaximumContractMaturityPeriodRange2_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl1">Maximum contract maturity period, range 2</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl2" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl2">Maximum contract maturity period, range 2</link:label>
    <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-20231231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange1" xlink:to="ions_MaximumContractMaturityPeriodRange1_lbl" xlink:title="label: MaximumContractMaturityPeriodRange1 to ions_MaximumContractMaturityPeriodRange1_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl1">Maximum contract maturity period, range 1</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange1" xlink:to="ions_MaximumContractMaturityPeriodRange1_lbl1" xlink:title="label: MaximumContractMaturityPeriodRange1 to ions_MaximumContractMaturityPeriodRange1_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl2" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl2">Maximum contract maturity period, range 1</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange1" xlink:to="ions_MaximumContractMaturityPeriodRange1_lbl2" xlink:title="label: MaximumContractMaturityPeriodRange1 to ions_MaximumContractMaturityPeriodRange1_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3_lbl" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumContractMaturityPeriodRange3_lbl1" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3_lbl1">Maximum contract maturity period, range 3</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3_lbl1" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumContractMaturityPeriodRange3_lbl2" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3_lbl2">Maximum contract maturity period, range 3</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3_lbl2" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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:loc xlink:type="locator" xlink:href="ions-20231231.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:loc xlink:type="locator" xlink:href="ions-20231231.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:loc xlink:type="locator" xlink:href="ions-20231231.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>
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    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl1" />
    <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-20231231.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, after One Through Two Years, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl1" />
    <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-20231231.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 [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-20231231.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-20231231.xsd#ions_AstraZenecaCollaborationWainuaMember" xlink:label="AstraZenecaCollaborationWainuaMember" xlink:title="AstraZenecaCollaborationWainuaMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstraZenecaCollaborationWainuaMember_lbl" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember_lbl">Collaboration agreement entered into with AstraZeneca PLC in December 2021 to develop and commercialize WAINUA. WAINUA (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="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember_lbl" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstraZenecaCollaborationWainuaMember_lbl1" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember_lbl1">AstraZeneca Collaboration, WAINUA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember_lbl1" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_AstraZenecaCollaborationWainuaMember_lbl2" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember_lbl2">WAINUA (Eplontersen) [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember_lbl2" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AstraZenecaCollaborationWainuaMember_lbl3" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember_lbl3">WAINUA (Eplontersen) Collaboration with AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember_lbl3" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.xsd#ions_OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:label="OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:title="OtsukaPharmaceuticalCoLtdCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl" xml:lang="en-US" id="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl">Collaboration agreement entered into with Otsuka Pharmaceutical Co., Ltd. (Otsuka) in December 2023 to develop and commercialize donidalorsen, an investigational ligand-conjugated antisense (LICA) medicine designed to target the prekallikrein (PKK) pathway.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:to="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl" xlink:title="label: OtsukaPharmaceuticalCoLtdCollaborationMember to ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl1" xml:lang="en-US" id="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl1">Otsuka Pharmaceutical Co., Ltd. Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:to="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl1" xlink:title="label: OtsukaPharmaceuticalCoLtdCollaborationMember to ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl2" xml:lang="en-US" id="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl2">Otsuka [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtsukaPharmaceuticalCoLtdCollaborationMember" xlink:to="ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl2" xlink:title="label: OtsukaPharmaceuticalCoLtdCollaborationMember to ions_OtsukaPharmaceuticalCoLtdCollaborationMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.xsd#ions_SwedishOrphanBiovitrumABDistributionAgreementMember" xlink:label="SwedishOrphanBiovitrumABDistributionAgreementMember" xlink:title="SwedishOrphanBiovitrumABDistributionAgreementMember" />
    <link:label xlink:type="resource" xlink:label="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl" xml:lang="en-US" id="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl">Distribution agreement with Swedish Orphan Biovitrum AB (Sobi) to commercialize TEGSEDI and WAYLIVRA in Europe in January 2021 and TEGSEDI in North America in April 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SwedishOrphanBiovitrumABDistributionAgreementMember" xlink:to="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl" xlink:title="label: SwedishOrphanBiovitrumABDistributionAgreementMember to ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl1" xml:lang="en-US" id="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl1">Swedish Orphan Biovitrum AB Distribution Agreement [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SwedishOrphanBiovitrumABDistributionAgreementMember" xlink:to="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl1" xlink:title="label: SwedishOrphanBiovitrumABDistributionAgreementMember to ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl2" xml:lang="en-US" id="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl2">Sobi [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SwedishOrphanBiovitrumABDistributionAgreementMember" xlink:to="ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl2" xlink:title="label: SwedishOrphanBiovitrumABDistributionAgreementMember to ions_SwedishOrphanBiovitrumABDistributionAgreementMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_NumberOfEarlyStagePrograms" xlink:label="NumberOfEarlyStagePrograms" xlink:title="NumberOfEarlyStagePrograms" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfEarlyStagePrograms_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfEarlyStagePrograms_lbl" xml:lang="en-US" id="ions_NumberOfEarlyStagePrograms_lbl">Number of early-stage programs to be developed for RNA-targeting investigational medicines for the treatment of Alzheimer's disease (AD) and Huntington's disease (HD).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfEarlyStagePrograms" xlink:to="ions_NumberOfEarlyStagePrograms_lbl" xlink:title="label: NumberOfEarlyStagePrograms to ions_NumberOfEarlyStagePrograms_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfEarlyStagePrograms_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfEarlyStagePrograms_lbl1" xml:lang="en-US" id="ions_NumberOfEarlyStagePrograms_lbl1">Number of early-stage programs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfEarlyStagePrograms" xlink:to="ions_NumberOfEarlyStagePrograms_lbl1" xlink:title="label: NumberOfEarlyStagePrograms to ions_NumberOfEarlyStagePrograms_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember" xlink:label="ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember" xlink:title="ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl">Research and development (R&amp;D) services for the investigational medicine for Huntington's Disease (HD).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember" xlink:to="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember to ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl1">Research and Development Services for Investigational Medicine for Huntington's Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember" xlink:to="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember to ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl2">R&amp;D Services for Investigational Medicine for HD [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember" xlink:to="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember to ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.xsd#ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" xlink:label="ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" xlink:title="ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl">Research and development (R&amp;D) services for the investigational medicine for Alzheimer's Disease (AD).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" xlink:to="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember to ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl1">Research and Development Services for Investigational Medicine for Alzheimer's Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" xlink:to="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember to ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl2">R&amp;D Services for Investigational Medicine for AD [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember" xlink:to="ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember to ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_RocheCollaborationRNATargetedProgramsForADAndHDMember" xlink:label="RocheCollaborationRNATargetedProgramsForADAndHDMember" xlink:title="RocheCollaborationRNATargetedProgramsForADAndHDMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl">Collaboration agreement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in September 2023 to develop two undisclosed early-stage programs for RNA-targeting investigational medicines for the treatment of Alzheimer's disease (AD) and Huntington's disease (HD).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationRNATargetedProgramsForADAndHDMember" xlink:to="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl" xlink:title="label: RocheCollaborationRNATargetedProgramsForADAndHDMember to ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl1" xml:lang="en-US" id="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl1">Roche Collaboration, RNA-targeted Programs for AD and HD [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationRNATargetedProgramsForADAndHDMember" xlink:to="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl1" xlink:title="label: RocheCollaborationRNATargetedProgramsForADAndHDMember to ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl2" xml:lang="en-US" id="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl2">RNA-targeted Programs for AD and HD [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationRNATargetedProgramsForADAndHDMember" xlink:to="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl2" xlink:title="label: RocheCollaborationRNATargetedProgramsForADAndHDMember to ions_RocheCollaborationRNATargetedProgramsForADAndHDMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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" />
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    <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-20231231.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">HD [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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_QalsodyMember" xlink:label="QalsodyMember" xlink:title="QalsodyMember" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_QalsodyMember_lbl" xml:lang="en-US" id="ions_QalsodyMember_lbl">Tofersen (IONIS-SOD1Rx or BIIB067), or QALSODY, 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="QalsodyMember" xlink:to="ions_QalsodyMember_lbl" xlink:title="label: QalsodyMember to ions_QalsodyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_QalsodyMember_lbl1" xml:lang="en-US" id="ions_QalsodyMember_lbl1">QALSODY [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyMember" xlink:to="ions_QalsodyMember_lbl1" xlink:title="label: QalsodyMember to ions_QalsodyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_QalsodyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_QalsodyMember_lbl2" xml:lang="en-US" id="ions_QalsodyMember_lbl2">QALSODY [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QalsodyMember" xlink:to="ions_QalsodyMember_lbl2" xlink:title="label: QalsodyMember to ions_QalsodyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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>
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    <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-20231231.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>
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    <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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_AttrvPnMember" xlink:label="AttrvPnMember" xlink:title="AttrvPnMember" />
    <link:label xlink:type="resource" xlink:label="ions_AttrvPnMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AttrvPnMember_lbl" xml:lang="en-US" id="ions_AttrvPnMember_lbl">ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AttrvPnMember" xlink:to="ions_AttrvPnMember_lbl" xlink:title="label: AttrvPnMember to ions_AttrvPnMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AttrvPnMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AttrvPnMember_lbl1" xml:lang="en-US" id="ions_AttrvPnMember_lbl1">ATTRv-PN [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AttrvPnMember" xlink:to="ions_AttrvPnMember_lbl1" xlink:title="label: AttrvPnMember to ions_AttrvPnMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AttrvPnMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AttrvPnMember_lbl2" xml:lang="en-US" id="ions_AttrvPnMember_lbl2">ATTRv-PN [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AttrvPnMember" xlink:to="ions_AttrvPnMember_lbl2" xlink:title="label: AttrvPnMember to ions_AttrvPnMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_NovartisCollaborationsMember" xlink:label="NovartisCollaborationsMember" xlink:title="NovartisCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NovartisCollaborationsMember_lbl" xml:lang="en-US" id="ions_NovartisCollaborationsMember_lbl">Collaboration agreements entered into with Novartis International AG (Novartis).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationsMember" xlink:to="ions_NovartisCollaborationsMember_lbl" xlink:title="label: NovartisCollaborationsMember to ions_NovartisCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NovartisCollaborationsMember_lbl1" xml:lang="en-US" id="ions_NovartisCollaborationsMember_lbl1">Novartis Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationsMember" xlink:to="ions_NovartisCollaborationsMember_lbl1" xlink:title="label: NovartisCollaborationsMember to ions_NovartisCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NovartisCollaborationsMember_lbl2" xml:lang="en-US" id="ions_NovartisCollaborationsMember_lbl2">Novartis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationsMember" xlink:to="ions_NovartisCollaborationsMember_lbl2" xlink:title="label: NovartisCollaborationsMember to ions_NovartisCollaborationsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.xsd#ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:label="NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:title="NovartisCollaborationLpADrivenCardiovascularDiseaseMember" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl" xml:lang="en-US" id="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl">Collaboration agreement entered into with Novartis International AG (Novartis) in August 2023 for the discovery, development and commercialization of a novel medicine for patients with lipoprotein(a), or Lp(a)-driven cardiovascular disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:to="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl" xlink:title="label: NovartisCollaborationLpADrivenCardiovascularDiseaseMember to ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl1" xml:lang="en-US" id="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl1">Novartis Collaboration, Lp(a)-Driven Cardiovascular Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:to="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl1" xlink:title="label: NovartisCollaborationLpADrivenCardiovascularDiseaseMember to ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl2" xml:lang="en-US" id="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl2">Lp(a)-Driven Cardiovascular Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationLpADrivenCardiovascularDiseaseMember" xlink:to="ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl2" xlink:title="label: NovartisCollaborationLpADrivenCardiovascularDiseaseMember to ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.xsd#ions_NovartisCollaborationPelacarsenMember" xlink:label="NovartisCollaborationPelacarsenMember" xlink:title="NovartisCollaborationPelacarsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationPelacarsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NovartisCollaborationPelacarsenMember_lbl" xml:lang="en-US" id="ions_NovartisCollaborationPelacarsenMember_lbl">Collaboration agreement entered into with Novartis International AG (Novartis) in January 2017 to develop and commercialize pelacarsen.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationPelacarsenMember" xlink:to="ions_NovartisCollaborationPelacarsenMember_lbl" xlink:title="label: NovartisCollaborationPelacarsenMember to ions_NovartisCollaborationPelacarsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationPelacarsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NovartisCollaborationPelacarsenMember_lbl1" xml:lang="en-US" id="ions_NovartisCollaborationPelacarsenMember_lbl1">Novartis Collaboration, Pelacarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationPelacarsenMember" xlink:to="ions_NovartisCollaborationPelacarsenMember_lbl1" xlink:title="label: NovartisCollaborationPelacarsenMember to ions_NovartisCollaborationPelacarsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationPelacarsenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NovartisCollaborationPelacarsenMember_lbl2" xml:lang="en-US" id="ions_NovartisCollaborationPelacarsenMember_lbl2">Pelacarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationPelacarsenMember" xlink:to="ions_NovartisCollaborationPelacarsenMember_lbl2" xlink:title="label: NovartisCollaborationPelacarsenMember to ions_NovartisCollaborationPelacarsenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:label="PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:title="PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl">The potential premium received if common stock was 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="PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl" xlink:title="label: PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture to ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl1" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl1">Potential premium received if common stock was purchased in future</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl1" xlink:title="label: PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture to ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl2" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl2">Potential premium received if common stock was purchased in the future</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl2" xlink:title="label: PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture to ions_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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-20231231.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 medicine</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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.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-20231231.xsd#ions_AccruedClinicalDevelopmentExpenses" xlink:label="AccruedClinicalDevelopmentExpenses" xlink:title="AccruedClinicalDevelopmentExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalDevelopmentExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedClinicalDevelopmentExpenses_lbl" xml:lang="en-US" id="ions_AccruedClinicalDevelopmentExpenses_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for clinical development 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="AccruedClinicalDevelopmentExpenses" xlink:to="ions_AccruedClinicalDevelopmentExpenses_lbl" xlink:title="label: AccruedClinicalDevelopmentExpenses to ions_AccruedClinicalDevelopmentExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalDevelopmentExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedClinicalDevelopmentExpenses_lbl1" xml:lang="en-US" id="ions_AccruedClinicalDevelopmentExpenses_lbl1">Accrued clinical development expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalDevelopmentExpenses" xlink:to="ions_AccruedClinicalDevelopmentExpenses_lbl1" xlink:title="label: AccruedClinicalDevelopmentExpenses to ions_AccruedClinicalDevelopmentExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalDevelopmentExpenses_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_AccruedClinicalDevelopmentExpenses_lbl2" xml:lang="en-US" id="ions_AccruedClinicalDevelopmentExpenses_lbl2">Clinical expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalDevelopmentExpenses" xlink:to="ions_AccruedClinicalDevelopmentExpenses_lbl2" xlink:title="label: AccruedClinicalDevelopmentExpenses to ions_AccruedClinicalDevelopmentExpenses_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20231231.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" />
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<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
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end
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<DOCUMENT>
<TYPE>GRAPHIC
<SEQUENCE>21
<FILENAME>image06.jpg
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<SEQUENCE>27
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<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Feb. 15, 2024</div></th>
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<td class="text">0000874015<span></span>
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<td class="text">33-0336973<span></span>
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<td class="text">2855 Gazelle Court<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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_DocumentFinStmtErrorCorrectionFlag', window );">Document Financial Statement Error Correction [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="re">
<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="ro">
<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">$ 4,243,321,410<span></span>
</td>
</tr>
<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_EntityCommonStockSharesOutstanding', window );">Entity Common Stock, Shares Outstanding</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">145,751,797<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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_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="re">
<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="ro">
<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>
</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_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_DocumentFinStmtErrorCorrectionFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 whether any of the financial statement period in the filing include a restatement due to error correction.</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-K<br> -Number 229<br> -Section 402<br> -Subsection w<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 3: 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 4: 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_DocumentFinStmtErrorCorrectionFlag</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>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989539468432">
<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, 2023</div></th>
<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_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">$ 399,266<span></span>
</td>
<td class="nump">$ 276,472<span></span>
</td>
</tr>
<tr class="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">1,931,935<span></span>
</td>
<td class="nump">1,710,397<span></span>
</td>
</tr>
<tr class="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">97,778<span></span>
</td>
<td class="nump">25,538<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_InventoryNet', window );">Inventories</a></td>
<td class="nump">28,425<span></span>
</td>
<td class="nump">22,033<span></span>
</td>
</tr>
<tr class="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">184,449<span></span>
</td>
<td class="nump">168,254<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">2,641,853<span></span>
</td>
<td class="nump">2,202,694<span></span>
</td>
</tr>
<tr class="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">71,043<span></span>
</td>
<td class="nump">74,294<span></span>
</td>
</tr>
<tr class="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">171,896<span></span>
</td>
<td class="nump">181,544<span></span>
</td>
</tr>
<tr class="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">105,280<span></span>
</td>
<td class="nump">75,344<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">2,990,072<span></span>
</td>
<td class="nump">2,533,876<span></span>
</td>
</tr>
<tr class="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">26,027<span></span>
</td>
<td class="nump">17,921<span></span>
</td>
</tr>
<tr class="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">67,727<span></span>
</td>
<td class="nump">49,178<span></span>
</td>
</tr>
<tr class="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">147,894<span></span>
</td>
<td class="nump">140,101<span></span>
</td>
</tr>
<tr class="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">2,151<span></span>
</td>
<td class="nump">6,249<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtCurrent', window );">0.125 percent convertible senior notes, net</a></td>
<td class="nump">44,332<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_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred contract revenue</a></td>
<td class="nump">151,128<span></span>
</td>
<td class="nump">90,577<span></span>
</td>
</tr>
<tr class="re">
<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">8,831<span></span>
</td>
<td class="nump">7,535<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_LiabilitiesCurrent', window );">Total current liabilities</a></td>
<td class="nump">448,090<span></span>
</td>
<td class="nump">311,561<span></span>
</td>
</tr>
<tr class="re">
<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">241,184<span></span>
</td>
<td class="nump">287,768<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_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Liability related to sale of future royalties, net</a></td>
<td class="nump">513,736<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_OperatingLeaseLiabilityNoncurrent', window );">Long-term lease liabilities</a></td>
<td class="nump">170,875<span></span>
</td>
<td class="nump">178,941<span></span>
</td>
</tr>
<tr class="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 obligations</a></td>
<td class="nump">41,836<span></span>
</td>
<td class="nump">15,973<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_Liabilities', window );">Total liabilities</a></td>
<td class="nump">2,603,386<span></span>
</td>
<td class="nump">1,960,989<span></span>
</td>
</tr>
<tr class="ro">
<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="re">
<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, 144,340,526 and 142,057,736 shares issued and outstanding at December 31, 2023 and December 31, 2022, respectively</a></td>
<td class="nump">144<span></span>
</td>
<td class="nump">142<span></span>
</td>
</tr>
<tr class="ro">
<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">2,215,098<span></span>
</td>
<td class="nump">2,059,850<span></span>
</td>
</tr>
<tr class="re">
<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">(32,645)<span></span>
</td>
<td class="num">(57,480)<span></span>
</td>
</tr>
<tr class="ro">
<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">(1,795,911)<span></span>
</td>
<td class="num">(1,429,625)<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_StockholdersEquity', window );">Total stockholders' equity</a></td>
<td class="nump">386,686<span></span>
</td>
<td class="nump">572,887<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_LiabilitiesAndStockholdersEquity', window );">Total liabilities and stockholders' equity</a></td>
<td class="nump">2,990,072<span></span>
</td>
<td class="nump">2,533,876<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_ConvertibleSeniorNotes175PercentMember', window );">1.75 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">562,285<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_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">625,380<span></span>
</td>
<td class="nump">622,242<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">$ 0<span></span>
</td>
<td class="nump">$ 544,504<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 the unamortized liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate 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_LiabilityRelatedToSaleOfFutureRoyaltiesNet</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_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://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481372/852-10-55-10<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(15)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<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;">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> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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>Amount, after tax, of accumulated increase (decrease) in equity from transaction and other event and circumstance from nonowner source.</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> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14A<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482790/220-10-45-14A<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482790/220-10-45-11<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480016/944-40-65-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480016/944-40-65-2<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482790/220-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_AdditionalPaidInCapitalCommonStock</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:monetaryItemType</td>
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<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>
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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>
</tr>
<tr>
<td style="padding-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_AssetsCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_AssetsCurrentAbstract</td>
</tr>
<tr>
<td style="padding-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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483467/210-10-45-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(22))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-2<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;">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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-2<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;">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_ConvertibleDebtCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 the carrying value of long-term convertible debt as of the balance sheet date that is scheduled to be repaid within one year or in the normal operating cycle if longer. Convertible debt is a financial 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(19))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_ConvertibleDebtCurrent</td>
</tr>
<tr>
<td style="padding-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> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483467/210-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481203/810-10-50-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481231/810-10-45-25<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (bb)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481203/810-10-50-3<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_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>
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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_LiabilitiesAndStockholdersEquity</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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<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<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_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>
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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>
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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>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>
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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>
</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> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(13)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<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;">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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479041/842-20-45-1<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;">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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479041/842-20-45-1<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;">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/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(17))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481372/852-10-55-10<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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_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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 360<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482099/360-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481372/852-10-55-10<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 360<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480842/942-360-50-1<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;">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>Amount of accumulated undistributed earnings (deficit).</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> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480016/944-40-65-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480016/944-40-65-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480990/946-20-50-11<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(17))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480008/505-10-S99-1<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(5))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<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;">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>Amount of equity (deficit) attributable to parent. Excludes temporary equity and equity 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">
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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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538571632">
<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, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</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_StockholdersEquityAbstract', window );"><strong>Stockholders' equity:</strong></a></td>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 0.001<span></span>
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<td class="nump">$ 0.001<span></span>
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<td class="nump">300,000,000<span></span>
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<td class="nump">300,000,000<span></span>
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<td class="nump">144,340,526<span></span>
</td>
<td class="nump">142,057,736<span></span>
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<td class="nump">144,340,526<span></span>
</td>
<td class="nump">142,057,736<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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75 Percent Convertible Senior Notes [Member]</a></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_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></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_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<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_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</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_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></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_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
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<td class="nump">0.00%<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_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</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="nump">0.125%<span></span>
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<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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br></p></div>
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<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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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>
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<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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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">
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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 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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481112/505-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.6-05(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-2<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-3<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(7))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-3<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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_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> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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>
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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_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>
</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>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_StockholdersEquityAbstract</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>
</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_ConvertibleSeniorNotes175PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ConvertibleSeniorNotes175PercentMember</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>
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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>
<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>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989541106464">
<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, 2023</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_RevenueFromContractWithCustomerAbstract', 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">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<span></span>
</td>
</tr>
<tr class="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">9,133<span></span>
</td>
<td class="nump">14,116<span></span>
</td>
<td class="nump">10,842<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">899,625<span></span>
</td>
<td class="nump">833,147<span></span>
</td>
<td class="nump">643,453<span></span>
</td>
</tr>
<tr class="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">232,619<span></span>
</td>
<td class="nump">150,295<span></span>
</td>
<td class="nump">186,347<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">1,141,377<span></span>
</td>
<td class="nump">997,558<span></span>
</td>
<td class="nump">840,642<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">(353,730)<span></span>
</td>
<td class="num">(410,191)<span></span>
</td>
<td class="num">(30,186)<span></span>
</td>
</tr>
<tr class="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">89,041<span></span>
</td>
<td class="nump">25,331<span></span>
</td>
<td class="nump">10,044<span></span>
</td>
</tr>
<tr class="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">(12,660)<span></span>
</td>
<td class="num">(8,122)<span></span>
</td>
<td class="num">(9,349)<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_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties', window );">Interest expense related to sale of future royalties</a></td>
<td class="num">(68,797)<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_GainLossOnInvestments', window );">Gain (loss) on investments</a></td>
<td class="num">(1,914)<span></span>
</td>
<td class="num">(7,333)<span></span>
</td>
<td class="nump">10,103<span></span>
</td>
</tr>
<tr class="ro">
<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 (loss) on sale of real estate assets</a></td>
<td class="num">(161)<span></span>
</td>
<td class="nump">149,604<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_OtherNonoperatingIncomeExpense', window );">Other income (expense)</a></td>
<td class="nump">14,256<span></span>
</td>
<td class="num">(7,274)<span></span>
</td>
<td class="num">(9,760)<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">(333,965)<span></span>
</td>
<td class="num">(257,985)<span></span>
</td>
<td class="num">(29,148)<span></span>
</td>
</tr>
<tr class="re">
<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">(32,321)<span></span>
</td>
<td class="num">(11,737)<span></span>
</td>
<td class="nump">551<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_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (366,286)<span></span>
</td>
<td class="num">$ (269,722)<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_EarningsPerShareBasic', window );">Basic net loss per share (in dollars per share)</a></td>
<td class="num">$ (2.56)<span></span>
</td>
<td class="num">$ (1.9)<span></span>
</td>
<td class="num">$ (0.2)<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_WeightedAverageNumberOfSharesOutstandingBasic', window );">Shares used in computing basic net loss per share (in shares)</a></td>
<td class="nump">143,190<span></span>
</td>
<td class="nump">141,848<span></span>
</td>
<td class="nump">141,021<span></span>
</td>
</tr>
<tr class="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 loss per share (in dollars per share)</a></td>
<td class="num">$ (2.56)<span></span>
</td>
<td class="num">$ (1.9)<span></span>
</td>
<td class="num">$ (0.2)<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_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net loss per share (in shares)</a></td>
<td class="nump">143,190<span></span>
</td>
<td class="nump">141,848<span></span>
</td>
<td class="nump">141,021<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="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:</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">$ 308,591<span></span>
</td>
<td class="nump">$ 303,358<span></span>
</td>
<td class="nump">$ 342,395<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="re">
<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:</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">240,379<span></span>
</td>
<td class="nump">242,314<span></span>
</td>
<td class="nump">267,776<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_OtherCommercialMember', window );">Other 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="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:</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">68,212<span></span>
</td>
<td class="nump">61,044<span></span>
</td>
<td class="nump">74,619<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_RevenueFromContractWithCustomerAbstract', 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">479,056<span></span>
</td>
<td class="nump">284,009<span></span>
</td>
<td class="nump">468,061<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_RevenueFromContractWithCustomerAbstract', 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">352,657<span></span>
</td>
<td class="nump">207,222<span></span>
</td>
<td class="nump">468,061<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_WainuaJointDevelopmentRevenueMember', window );">WAINUA 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_RevenueFromContractWithCustomerAbstract', 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">$ 126,399<span></span>
</td>
<td class="nump">$ 76,787<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_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 expense using the effective interest rate method and amortization of issuance costs related to the sale of future royalties.</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_InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties</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_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> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479941/924-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.2(a),(d))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<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;">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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<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;">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> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 15<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482635/260-10-55-15<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 815<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480175/815-40-65-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 815<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480175/815-40-65-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-11<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-11<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-7<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-2<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-60B<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-4<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482662/260-10-50-1<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-10<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483589/942-220-S99-1<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<br><br>Reference 16: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 52<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482635/260-10-55-52<br><br>Reference 17: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-7<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 15<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482635/260-10-55-15<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 815<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480175/815-40-65-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 815<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480175/815-40-65-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-11<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-11<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-7<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-2<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-60B<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-4<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482662/260-10-50-1<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483589/942-220-S99-1<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<br><br>Reference 15: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 52<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482635/260-10-55-52<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-7<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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://www.xbrl.org/2003/role/recommendedDisclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.7(c),9(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<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;">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> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(11))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 5: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 31<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-31<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 235<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479557/942-235-S99-1<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 25<br> -Paragraph 1<br> -SubTopic 20<br> -Topic 940<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481913/940-20-25-1<br><br>Reference 9: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(10))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<br><br>Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(15))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483589/942-220-S99-1<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;">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> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-8<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-9<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-10<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -SubTopic 20<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482659/740-20-45-2<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -SubTopic 10<br> -Topic 235<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<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;">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/exampleRef<br> -Topic 946<br> -SubTopic 830<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480167/946-830-55-10<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 3<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483581/946-220-45-3<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-07(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482925/835-30-45-3<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04.9)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483589/942-220-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (210.5-03(11))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483013/835-20-50-1<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;">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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.8)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.7(a),(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<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;">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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 323<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481687/323-10-50-3<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-28<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_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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<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>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NonoperatingIncomeExpenseAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_NonoperatingIncomeExpenseAbstract</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>
</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_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>
<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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 31<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-31<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
<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_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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.9)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<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;">us-gaap_OtherNonoperatingIncomeExpense</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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</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_RevenueFromContractWithCustomerAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_RevenueFromContractWithCustomerAbstract</td>
</tr>
<tr>
<td style="padding-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>
</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> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479941/924-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-5<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-40<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-41<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<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;">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> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482662/260-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 16<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-16<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482662/260-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-10<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_CommercialMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_CommercialMember</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>
<td></td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_SpinrazaRoyaltiesMember</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_ProductOrServiceAxis=ions_OtherCommercialMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_OtherCommercialMember</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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<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>
<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>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_CollaborativeAgreementRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_CollaborativeAgreementRevenueMember</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>
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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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_WainuaJointDevelopmentRevenueMember</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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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989543279248">
<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, 2023</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_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>
</tr>
<tr class="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="num">$ (366,286)<span></span>
</td>
<td class="num">$ (269,722)<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 );">Unrealized gains (losses) on investments, net of tax</a></td>
<td class="nump">24,484<span></span>
</td>
<td class="num">(24,395)<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 );">Currency translation adjustment</a></td>
<td class="nump">351<span></span>
</td>
<td class="num">(417)<span></span>
</td>
<td class="num">(111)<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_ComprehensiveIncomeNetOfTax', window );">Comprehensive loss</a></td>
<td class="num">$ (341,451)<span></span>
</td>
<td class="num">$ (294,534)<span></span>
</td>
<td class="num">$ (40,194)<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_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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(24))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(26))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483589/942-220-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(22))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482790/220-10-45-1A<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482790/220-10-45-1B<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482790/220-10-45-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
<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>
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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 adjustment, of gain (loss) in value of unsold investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), attributable to 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> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 19<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481231/810-10-45-19<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 20<br> -SubTopic 10<br> -Topic 810<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481231/810-10-45-20<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(3)<br> -SubTopic 10<br> -Topic 810<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481203/810-10-50-1A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (a-c)<br> -SubTopic 10<br> -Topic 220<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482790/220-10-45-10A<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482790/220-10-45-11<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481839/830-10-45-9<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 35<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482014/830-20-35-3<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481694/830-30-45-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_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>35
<FILENAME>R6.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989536999248">
<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</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_StockholdersEquity', 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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</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_StockholdersEquity', 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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</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_StockholdersEquity', 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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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">(366,286)<span></span>
</td>
<td class="num">(366,286)<span></span>
</td>
</tr>
<tr class="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">24,484<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">24,484<span></span>
</td>
</tr>
<tr class="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">351<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">351<span></span>
</td>
</tr>
<tr class="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">$ 2<span></span>
</td>
<td class="nump">49,439<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">49,441<span></span>
</td>
</tr>
<tr class="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">2,283<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">105,809<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">105,809<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_StockholdersEquity', window );">Balance at Dec. 31, 2023</a></td>
<td class="nump">$ 144<span></span>
</td>
<td class="nump">$ 2,215,098<span></span>
</td>
<td class="num">$ (32,645)<span></span>
</td>
<td class="num">$ (1,795,911)<span></span>
</td>
<td class="nump">$ 386,686<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, 2023</a></td>
<td class="nump">144,341<span></span>
</td>
<td class="text">&#160;<span></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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 35<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480483/718-10-35-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 13<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481089/718-20-55-13<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481089/718-20-55-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481112/505-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480008/505-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 25<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481284/470-20-25-2<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;">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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 323<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481687/323-10-50-3<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-28<br><br>Reference 4: 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-Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(18))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 17: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-07(9))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-1<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(1)(d))<br> -Publisher FASB<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_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 adjustment, of gain (loss) in value of unsold investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), attributable to 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> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 19<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481231/810-10-45-19<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 20<br> -SubTopic 10<br> -Topic 810<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481231/810-10-45-20<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(3)<br> -SubTopic 10<br> -Topic 810<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481203/810-10-50-1A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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>
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<tr>
<td><strong> Period Type:</strong></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_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://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (a-c)<br> -SubTopic 10<br> -Topic 220<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482790/220-10-45-10A<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482790/220-10-45-11<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481839/830-10-45-9<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 35<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482014/830-20-35-3<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481694/830-30-45-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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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<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>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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481112/505-10-50-2<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;">us-gaap_SharesIssued</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:sharesItemType</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>instant</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>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>
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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_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>
<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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481112/505-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480008/505-10-S99-1<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation</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: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>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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, 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>
</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>
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<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>Amount of equity (deficit) attributable to parent. Excludes temporary equity and equity 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/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 946<br> -SubTopic 830<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480167/946-830-55-12<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(19))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.6-05(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-2<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-3<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-3<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(7))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-3<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 9: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 323<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481687/323-10-50-3<br><br>Reference 10: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-28<br><br>Reference 11: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 12: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(31))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 13: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 14: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 310<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 4.E)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480418/310-10-S99-2<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;">us-gaap_StockholdersEquity</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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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538357312">
<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="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2023</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_NetCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Operating 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>
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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_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (366,286)<span></span>
</td>
<td class="num">$ (269,722)<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_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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">10,292<span></span>
</td>
<td class="nump">14,328<span></span>
</td>
<td class="nump">15,487<span></span>
</td>
</tr>
<tr class="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="nump">9,647<span></span>
</td>
<td class="nump">5,362<span></span>
</td>
<td class="nump">1,721<span></span>
</td>
</tr>
<tr class="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="nump">2,559<span></span>
</td>
<td class="nump">2,415<span></span>
</td>
<td class="nump">2,352<span></span>
</td>
</tr>
<tr class="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 (discount) on investments, net</a></td>
<td class="num">(28,885)<span></span>
</td>
<td class="nump">7,389<span></span>
</td>
<td class="nump">17,776<span></span>
</td>
</tr>
<tr class="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="nump">6,330<span></span>
</td>
<td class="nump">5,373<span></span>
</td>
<td class="nump">4,958<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_RoyaltyPayments', window );">Non-cash royalty revenue related to sale of royalties</a></td>
<td class="num">(44,628)<span></span>
</td>
<td class="nump">0<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_InterestExpenseRelatedToSaleOfFutureRoyalties', window );">Non-cash interest related to sale of future royalties</a></td>
<td class="nump">68,238<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_ShareBasedCompensation', window );">Stock-based compensation expense</a></td>
<td class="nump">105,809<span></span>
</td>
<td class="nump">100,264<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_GainsLossesOnExtinguishmentOfDebt', window );">Loss (gain) on early retirement of debt</a></td>
<td class="num">(13,389)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">8,627<span></span>
</td>
</tr>
<tr class="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="nump">16,649<span></span>
</td>
<td class="nump">531<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_SaleAndLeasebackTransactionGainLossNet', window );">Loss (gain) on sale of real estate assets</a></td>
<td class="nump">161<span></span>
</td>
<td class="num">(150,135)<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_RealizedInvestmentGainsLosses', window );">Loss (gain) on investments</a></td>
<td class="nump">1,589<span></span>
</td>
<td class="nump">224<span></span>
</td>
<td class="num">(1,092)<span></span>
</td>
</tr>
<tr class="ro">
<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="nump">1,661<span></span>
</td>
<td class="nump">2,030<span></span>
</td>
<td class="nump">2,707<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="num">(72,059)<span></span>
</td>
<td class="nump">36,358<span></span>
</td>
<td class="nump">14,308<span></span>
</td>
</tr>
<tr class="re">
<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="num">(6,392)<span></span>
</td>
<td class="nump">2,773<span></span>
</td>
<td class="num">(2,841)<span></span>
</td>
</tr>
<tr class="ro">
<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="num">(29,840)<span></span>
</td>
<td class="num">(24,682)<span></span>
</td>
<td class="num">(877)<span></span>
</td>
</tr>
<tr class="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="nump">8,119<span></span>
</td>
<td class="nump">1,094<span></span>
</td>
<td class="num">(6,000)<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_IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable', window );">Income taxes</a></td>
<td class="num">(4,098)<span></span>
</td>
<td class="nump">6,213<span></span>
</td>
<td class="num">(280)<span></span>
</td>
</tr>
<tr class="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="nump">18,549<span></span>
</td>
<td class="nump">10,368<span></span>
</td>
<td class="num">(26,918)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherCurrentLiabilities', window );">Accrued liabilities and other current liabilities</a></td>
<td class="num">(5,506)<span></span>
</td>
<td class="nump">46,695<span></span>
</td>
<td class="num">(8,381)<span></span>
</td>
</tr>
<tr class="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="nump">13,967<span></span>
</td>
<td class="num">(71,248)<span></span>
</td>
<td class="num">(82,829)<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="num">(307,513)<span></span>
</td>
<td class="num">(274,370)<span></span>
</td>
<td class="nump">30,799<span></span>
</td>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="num">(1,770,814)<span></span>
</td>
<td class="num">(1,485,772)<span></span>
</td>
<td class="num">(1,124,193)<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_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities', window );">Proceeds from sale of short-term investments</a></td>
<td class="nump">1,584,676<span></span>
</td>
<td class="nump">989,152<span></span>
</td>
<td class="nump">1,344,185<span></span>
</td>
</tr>
<tr class="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="num">(23,805)<span></span>
</td>
<td class="num">(15,721)<span></span>
</td>
<td class="num">(11,955)<span></span>
</td>
</tr>
<tr class="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">22<span></span>
</td>
<td class="nump">254,083<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_PaymentsToAcquireIntangibleAssets', window );">Acquisition of licenses and other assets, net</a></td>
<td class="num">(4,206)<span></span>
</td>
<td class="num">(4,378)<span></span>
</td>
<td class="num">(5,946)<span></span>
</td>
</tr>
<tr class="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="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(7,185)<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="num">(214,127)<span></span>
</td>
<td class="num">(262,636)<span></span>
</td>
<td class="nump">194,906<span></span>
</td>
</tr>
<tr class="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>
</tr>
<tr class="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="nump">49,442<span></span>
</td>
<td class="nump">6,373<span></span>
</td>
<td class="nump">11,565<span></span>
</td>
</tr>
<tr class="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="nump">0<span></span>
</td>
<td class="num">(10,953)<span></span>
</td>
<td class="num">(16,725)<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_ProceedsFromSaleOfFutureRoyalties', window );">Proceeds from sale of future royalties</a></td>
<td class="nump">500,000<span></span>
</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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Payments of transaction costs related to sale of future royalties</a></td>
<td class="num">(10,434)<span></span>
</td>
<td class="num">(29)<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_ProceedsFromRealEstateTransaction', window );">Proceeds from real estate transaction</a></td>
<td class="nump">32,352<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_RepaymentsOfConvertibleDebt', window );">Repayment of remaining principal amount of 1 percent convertible senior notes at maturity</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(61,967)<span></span>
</td>
</tr>
<tr class="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="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">89,752<span></span>
</td>
</tr>
<tr class="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="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(136,620)<span></span>
</td>
</tr>
<tr class="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="num">(160)<span></span>
</td>
<td class="num">(50,686)<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_NetCashProvidedByUsedInFinancingActivities', window );">Net cash provided by (used in) financing activities</a></td>
<td class="nump">644,082<span></span>
</td>
<td class="num">(55,295)<span></span>
</td>
<td class="nump">245,933<span></span>
</td>
</tr>
<tr class="ro">
<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="nump">352<span></span>
</td>
<td class="num">(418)<span></span>
</td>
<td class="num">(111)<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_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect', window );">Net increase (decrease) in cash and cash equivalents</a></td>
<td class="nump">122,794<span></span>
</td>
<td class="num">(592,719)<span></span>
</td>
<td class="nump">471,527<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_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at beginning of year</a></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>
</tr>
<tr class="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 end of year</a></td>
<td class="nump">399,266<span></span>
</td>
<td class="nump">276,472<span></span>
</td>
<td class="nump">869,191<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="nump">6,512<span></span>
</td>
<td class="nump">2,898<span></span>
</td>
<td class="nump">4,778<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_IncomeTaxesPaid', window );">Income taxes paid</a></td>
<td class="nump">48,334<span></span>
</td>
<td class="nump">5,010<span></span>
</td>
<td class="nump">38<span></span>
</td>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="nump">0<span></span>
</td>
<td class="nump">168,931<span></span>
</td>
<td class="nump">6,641<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_NonCashCapitalAndPatentExpenditures', window );">Amounts accrued for capital and patent expenditures</a></td>
<td class="nump">172<span></span>
</td>
<td class="nump">4,767<span></span>
</td>
<td class="nump">705<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_ConvertibleSeniorNotes175PercentMember', window );">1.75 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>
</tr>
<tr class="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>
</tr>
<tr class="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 issuance of convertible senior notes</a></td>
<td class="nump">575,000<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_PaymentsOfDebtIssuanceCosts', window );">Convertible senior notes issuance costs</a></td>
<td class="num">(14,175)<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_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>
</tr>
<tr class="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>
</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_EarlyRepaymentOfConvertibleDebt', window );">Repurchase of convertible senior notes</a></td>
<td class="num">(487,943)<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_RepaymentsOfConvertibleDebt', window );">Repayment of remaining principal amount of 1 percent convertible senior notes at maturity</a></td>
<td class="num">(504,400)<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>
</tr>
<tr class="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>
</tr>
<tr class="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 issuance of convertible senior notes</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">632,500<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_PaymentsOfDebtIssuanceCosts', window );">Convertible senior notes issuance costs</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(15,609)<span></span>
</td>
</tr>
<tr class="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">89,800<span></span>
</td>
</tr>
<tr class="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="num">(136,700)<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
</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_EarlyRepaymentOfConvertibleDebt', window );">Repurchase of convertible senior notes</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(256,963)<span></span>
</td>
</tr>
<tr class="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 );">Repayment of remaining principal amount of 1 percent convertible senior notes at maturity</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (309,900)<span></span>
</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_InterestExpenseRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 expense using the effective interest rate method related to the sale of future royalties.</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_InterestExpenseRelatedToSaleOfFutureRoyalties</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_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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 for transaction costs 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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties</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_ProceedsFromRealEstateTransaction">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 transfer of legal ownership of two lots of undeveloped land to 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_ProceedsFromRealEstateTransaction</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_ProceedsFromSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 future royalties under a 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_ProceedsFromSaleOfFutureRoyalties</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_RoyaltyPayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 royalty payments made during the period under a 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_RoyaltyPayments</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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1F<br> -Subparagraph (b)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1F<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482925/835-30-45-3<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<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;">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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482686/350-30-45-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482665/350-30-50-2<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;">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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482913/230-10-50-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-24<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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>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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-24<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -SubTopic 230<br> -Topic 830<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481877/830-230-45-1<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;">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_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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482099/360-10-50-1<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;">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> -Topic 830<br> -SubTopic 230<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481877/830-230-45-1<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;">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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 360<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482130/360-10-45-5<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 360<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482099/360-10-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481303/470-50-40-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481303/470-50-40-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 350<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482665/350-30-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482913/230-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-25<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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/2003/role/disclosureRef<br> -Topic 912<br> -SubTopic 310<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482312/912-310-45-11<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_IncreaseDecreaseInOtherCurrentLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 current 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://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOtherCurrentLiabilities</td>
</tr>
<tr>
<td style="padding-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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 17<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-17<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (e)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-25<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482913/230-10-50-2<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;">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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-24<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-24<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 24<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-24<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-25<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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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<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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
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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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 323<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481687/323-10-50-3<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-28<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_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_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 periodic reduction over lease term of carrying amount of 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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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>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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-15<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 27<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-27<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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</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 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> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (e)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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>duration</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>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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481830/320-10-45-11<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-13<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-11<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-13<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
<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_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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 13<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-13<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-13<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_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> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-14<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 718<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481830/320-10-45-11<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 11<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-11<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(3)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<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;">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> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 53<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479589/842-20-55-53<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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/exampleRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 53<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479589/842-20-55-53<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-4<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479741/842-40-50-2<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;">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>
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<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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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 );">- 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_SupplementalCashFlowInformationAbstract</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 );">- 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_ConvertibleSeniorNotes175PercentMember</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_ConvertibleSeniorNotes0125PercentMember</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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<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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</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>
<td>na</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 );">- 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>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989540989568">
<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, 2023</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, 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_ConvertibleSeniorNotes175PercentMember', window );">1.75 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_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">
<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">1.75%<span></span>
</td>
<td class="nump">1.75%<span></span>
</td>
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
</tr>
<tr class="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="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_DebtInstrumentRepurchasedFaceAmount', window );">Principal amount repurchased</a></td>
<td class="nump">$ 504.4<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="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_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="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>
<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="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>
</td>
</tr>
<tr class="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">
<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="text">&#160;<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>
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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_DebtInstrumentRepurchasedFaceAmount', window );">Principal amount repurchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 247.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 375.6<span></span>
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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>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> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_DebtInstrumentInterestRateStatedPercentage</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>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>
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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_NetCashProvidedByUsedInFinancingActivitiesAbstract</td>
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<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember</td>
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989545287376">
<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, 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_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Organization and Basis of Presentation [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_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
    wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;).</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;"><br/>
  </div>

<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 United States, or
    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 WAINUA 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 selling, general and administrative, or SG&amp;A, expense and research and development, or R&amp;D, 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>

    <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>

    <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>

    <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>

    <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>

    <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>

    <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 may 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. When a partner exercises its option to license a
      medicine that was not previously determined to be a material right at the inception of the agreement 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.</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>

    <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 that 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>

    <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>

    <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>

    <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>

    <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>

    <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>

    <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>

<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>

    <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 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>

    <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>

    <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>

<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>

    <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>

    <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>

    <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;">We recognize royalty revenue 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.</div>

<div><br/>
  </div>

<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 Swedish Orphan Biovitrum AB, or 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; 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>

    <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>

    <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>

    <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>

    <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>

    <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 Note 4, <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: 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, 2023,
    approximately 87.8 percent of our contracts receivables were from one significant customer. As of December 31, 2022, approximately 82.5 percent of our contracts receivables were from one
    significant customer.</div>

<div><br/>
  </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, 2023 and 2022, we recognized $78.2 million and $73.5 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 R&amp;D operations. We expense R&amp;D costs as we incur them. When we make payments for R&amp;D 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 R&amp;D expenses are costs associated with our partner agreements. In 2023, 2022 and 2021, patent expenses were $4.3 million, $4.7 million and $5.3 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="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 our net loss by our weighted-average number of common shares outstanding during the
    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;">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, 2023,
    2022 and 2021, 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 from the following would have had an anti-dilutive effect on net loss
    per share:</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;">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;</span></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;"><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>

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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;">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>

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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;"><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>

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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>

<div><br/>
  </div>

<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, 2023, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, would also have had an
    anti-dilutive effect on 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;">Additionally as of December 31, 2023, 2022 and 2021, we had warrants related to our 0% Notes and 0.125% 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><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 years ended
    December 31, 2023 and 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; 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 we 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 PRSUs we granted in 2020 through 2022, <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. These PRSU awards also included an alternative three-year payout mechanism, or the Alternative Calculation, under
    which we must calculate an alternative payout at the end of the final three-year measurement period assuming the only measurement period for all
    shares under the award was the three-year period. If the Alternative Calculation is greater than payouts under the sum of the three years, then such PRSU award will pay out to achieve the number of shares payable under the Alternative Calculation.</div>

<div><br/>
  </div>

<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 PRSUs we granted in 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period
    based on our relative TSR as compared to a peer group of companies and as measured at the end of the 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 200 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 Note 8, <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: 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><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="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="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 public and private biotechnology companies that we received as part
      of a technology license or partner agreement. At December 31, 2023, we held equity investments in three publicly traded companies and seven 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 publicly traded companies at their listed stock price. 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="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 we determine as the following (in years):</div>

<div><br/>
  </div>

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    <td style="width: 80.34%; vertical-align: bottom;"> </td>

    <td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Useful Lives</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; 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;">Computer software, laboratory, manufacturing and other equipment</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3 to 10</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15 to 40</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; 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;">Land improvements</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 15</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; 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;">Furniture and fixtures</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 10</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;">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;">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, 2023, we
    had three outstanding convertible senior notes, our 1.75% Notes, which mature in June 2028, our 0% Notes, which mature in April 2026, and
    our 0.125% Notes, which mature in December 2024. Refer to Note 7, <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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Liability Related to Sale of Future 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;">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 arrangements with Biogen and Novartis, respectively. Refer to Note 7, <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 the 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;">Under our agreement with Royalty Pharma, we record upfront payments and milestone payments we receive from the sale of future royalties as
    a liability, net of transaction costs. We record royalty payments made to Royalty Pharma as a reduction of the liability or accrued interest and amortize the transaction costs over the estimated life of the royalty stream. We account for the associated
    interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the related product and recognizes the related 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 calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense using our
    current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material
    change in our estimate, we will prospectively adjust the effective interest rate and the related interest expense.</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;">We operate 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.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recently Issued 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 November 2023, the Financial Accounting Standards Board, or FASB, issued updated guidance on segment reporting. The guidance requires
    public companies with a single reportable segment to provide all disclosures required under ASC 280, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Reporting</span>. In addition, the guidance
    requires public companies to include in interim reports all disclosures related to a reportable segment's profit or loss and assets that are currently required in annual reports. This update is effective for annual periods beginning after December 15,
    2023 and interim periods beginning after December 15, 2024. The guidance is applied on a retrospective basis for all periods presented in the financial statements, unless it is impracticable. Early adoption of this guidance is permitted. We currently
    plan to adopt the annual reporting requirements in our 2024 Annual Report on Form 10-K. We plan to adopt the interim reporting requirements in our Quarterly Report on Form 10-Q in the first quarter of 2025.</div>

<div><br/>
  </div>

<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 2023, the FASB issued updated guidance on income tax disclosures. The new guidance requires companies to provide additional
    disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions and unrecognized deferred tax
    liabilities. This update is effective for annual periods beginning after December 15, 2024. Early adoption of this guidance is permitted. We currently plan to adopt this guidance in our 2025 Annual Report on Form 10-K.</div>

<div><br/>
  </div>

<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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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2. Supplemental Financial Data</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;">Our inventory consisted of the following (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%;">


  <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;">2023</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>

  </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>
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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;">20,985</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;">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>

  </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;">1,809</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;">2,699</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </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;">22,794</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;">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>

  </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;">5,477</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;">2,109</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;">154</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;">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>

  </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;">28,425</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;">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>

  </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;">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;">Our property, plant and equipment 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;">2023</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>

  </tr>

  <tr>

    <td style="background-color: #CCEEFF; vertical-align: bottom; white-space: nowrap; width: 76%;">
          <div style="text-align: left; margin-left: 6.6pt; 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; width: 1%; 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;">79,885</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;">74,351</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: -2.4pt; 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; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">41,228</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;">41,158</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: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leasehold 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;">28,276</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;">28,357</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: -2.4pt; 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; 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;">9,844</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;">9,575</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">&#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;">159,233</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">153,441</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: -2.4pt; 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;" 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;">(96,759</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;">(87,716</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">&#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;">62,474</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;">65,725</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: -2.4pt; 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;" 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;">8,569</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;">8,569</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; margin-left: 33.6pt; 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; 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;">71,043</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;">74,294</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: 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>

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    <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>

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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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    <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;">30,051</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;">55,500</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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty 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;">33,299</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;">30,993</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;">19,119</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: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total other commercial revenue</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;">68,212</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;">61,044</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;">74,619</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: left; text-indent: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial 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;">308,591</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;">303,358</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;">342,395</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;">Research and development 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">&#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: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement 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;">352,657</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;">207,222</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;">468,061</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: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA joint development revenue</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;">126,399</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;">76,787</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: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development 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;">479,056</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;">284,009</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;">468,061</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: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</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;">787,647</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;">587,367</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;">810,456</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="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; font-weight: bold;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">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. We earn royalty revenue on net sales of
    QALSODY which is included in Licensing and other royalty 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: 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We earn commercial revenue from TEGSEDI and WAYLIVRA sales
      under our distribution agreements with </span>Sobi<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. In addition, we receive royalties from</span> PTC Therapeutics International Limited, or PTC, for TEGSEDI&#160; and WAYLIVRA
    sales. Refer to Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>, for details on our commercialization partnerships with Sobi and PTC.</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;"><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 variable 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 payment 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 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 who 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;">WAINUA (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 WAINUA
    for the treatment of transthyretin amyloidosis, or ATTR. We jointly developed and are preparing to commercialize WAINUA with AstraZeneca in the U.S. We initially granted AstraZeneca exclusive rights to commercialize WAINUA outside the U.S., except for
    certain Latin American countries. In July 2023, we expanded those rights to include 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 WAINUA 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 WAINUA 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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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989545249200">
<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>
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<tr><th class="th"><div>Dec. 31, 2023</div></th></tr>
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<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4. 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. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. Under our 2013 strategic neurology collaboration, Biogen developed QALSODY (tofersen), our medicine that received
    accelerated approval in the U.S. to treat patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS. In addition, we and Biogen are currently developing numerous other investigational medicines to treat neurodegenerative diseases,
    including medicines in development to treat people with amyotrophic lateral sclerosis, or ALS, SMA, Angelman Syndrome, or AS, Alzheimer&#8217;s disease, or AD, and Parkinson&#8217;s disease, or PD. 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, 2023, we
    have received nearly $3.8 billion from our Biogen collaborations, including payments to purchase our stock.</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 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, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we earned more than $</span>2.1<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in total revenue under our SPINRAZA collaboration, including more than $</span>1.6<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 2023, we entered into a royalty purchase agreement with Royalty Pharma in which Royalty Pharma receives 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 the U.S. Food and Drug Administration, or FDA, approval of pelacarsen, which Novartis is developing.
    Refer to Note 7, <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 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;">.</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;">At the commencement of this
      collaboration, we received a </span>$25 million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> upfront payment from Biogen. In </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2021</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Biogen
      exercised its option to license ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">306</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, a drug we
      discovered under this collaboration, for which </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">we earned a $</span>60<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee payment. We recognized this payment as revenue in full because</span> Biogen had full use of the license without any continuing involvement from us. 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. <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 ION</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">306</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, 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 $555 million if Biogen advances ION306, which is comprised of 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 from any product that Biogen successfully commercializes under this collaboration.</span> From inception through December 31, 2023, 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; 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 2018, we and Biogen entered into a strategic collaboration
      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 </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 targets</span>. In most cases, Biogen will be responsible for conducting IND-enabling toxicology studies for the selected medicine. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen has 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;">At the commencement of this collaboration, <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;">For each medicine under this 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. </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 from any product that Biogen successfully commercializes under this collaboration.</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. From inception through December 31, 2023, we have received nearly $1.1 billion in payments under this collaboration, including payments to purchase our stock. We will achieve the next payment of up to $15 million if Biogen licenses a medicine<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;">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, 2023,
    we have included $623 million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in upfront and milestone payments in
      the transaction price for our R&amp;D services performance obligation under this collaboration, including a $</span>7.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment we achieved in the fourth quarter of 2023. This milestone payment did not create a new performance obligation because it is part of our original R&amp;D services
      performance obligation. Therefore, we included this amount 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 2013, we and Biogen entered into a 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. In
    most cases, we are 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 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.</div>

<div><br/>
  </div>

<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 currently advancing four
    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 (QALSODY and ION541) and <span style="-sec-ix-hidden:Fact_7b05dc571fcb46f8bbbe0db51a44d460">a</span>
    medicine for multiple system atrophy (ION464). In 2018, Biogen exercised its option to license QALSODY, our medicine that received accelerated approval in April 2023 from the FDA for the treatment of adult patients with SOD1-ALS. As a result, Biogen is
    responsible for global development, regulatory and commercialization activities and costs for QALSODY.</div>

<div><br/>
  </div>

<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.</div>

<div><br/>
  </div>

<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 QALSODY, we are eligible to receive nearly $110 million, which is comprised of a $35 million license fee we received when Biogen
    licensed QALSODY from us in 2018, $18 million in development milestone payments and up to $55 million in regulatory milestone payments. In addition, we are eligible to receive tiered royalties ranging from 11 percent to 15 percent on net sales of QALSODY. We will achieve the next milestone
    payment for QALSODY of $20 million if the European Medicines Agency, or EMA, approves Biogen&#8217;s Marketing Authorization Application, or MAA,
    filing of QALSODY.</div>

<div><br/>
  </div>

<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 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 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, 2023, we have received more than $325 million in payments under our 2013 strategic neurology collaboration. We will achieve the next payment of $70 million if Biogen licenses 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 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;"> R&amp;D 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 period we generated the payment because we did not have any performance obligations for the
      respective payment. For example, in 2023, we earned a </span>$16&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">million








      milestone payment from Biogen when the FDA approved Biogen&#8217;s New Drug Application, or NDA, for QALSODY, which we recognized in full because we did not have any remaining 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 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 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="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. For each program under this
      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 license fee of up to $</span>70<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
      million, up to $</span>10<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestone
      payments and up to $</span>130<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone
      payments, 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, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span>230<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration, including $</span>39<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in milestone payments we received from Biogen for advancing ION582
      during 2023 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 $</span>70<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>million if Biogen licenses ION582 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;">When we commenced development for IONIS-MAPT<sub>Rx</sub> and ION582, we identified two separate performance obligations as our development work for each medicine. 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 obligations. In 2022, we completed our R&amp;D services performance obligation for IONIS-MAPT<sub>Rx</sub>. From inception through December 31, 2023, 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>. From inception through December 31, 2023, we have included $68 million in milestone payments in the transaction price for our ION582 development performance obligation, including $39 million in milestone payments we received from Biogen for advancing ION582 during 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;">During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in thousands, 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;">2023</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; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">350,146</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;">366,696</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;">428,784</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: 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;">44</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;">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>

  </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>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span>307.4<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>351.2<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;">WAINUA (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 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for
    the treatment of ATTR. In December 2023, the FDA approved eplontersen with the brand name, WAINUA, in the U.S. for ATTRv-PN. We are jointly developing and commercializing WAINUA with AstraZeneca in the U.S. We initially granted AstraZeneca exclusive
    rights to commercialize WAINUA outside the U.S., except for certain Latin American countries. In July 2023, we expanded those rights to include 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;"><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 $</span>3.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion, which is comprised of a $</span>200<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment, a $</span>20<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee, up to $</span>485<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development and approval milestone payments and up to $</span>2.9<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in sales milestone payments. The agreement includes territory-specific development,
      commercial and medical affairs cost-sharing provisions. In addition, we are eligible to receive up to mid-</span>20 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> royalties for sales in the U.S. and tiered royalties ranging from mid to high teens for sales outside the U.S. From inception through </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received nearly $</span>360<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration. We will achieve the next payment of $</span>30<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upon regulatory approval of WAINUA for ATTRv-PN in the EU 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;">We evaluated our WAINUA 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 in 2021. In 2023, we earned a $20 million license fee payment when we licensed rights to Latin America for WAINUA to AstraZeneca. We recognized these payments in full because we did not have any remaining performance
    obligations after we delivered the licenses 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 WAINUA 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. In 2023, we earned a $50 million milestone payment when the FDA approved WAINUA for ATTRv-PN in the
    U.S. We recognized this milestone payment in full as joint development revenue because we did not have any remaining performance obligations related to the milestone payment.</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 WAINUA, we have a collaboration with AstraZeneca focused on discovering and developing treatments for
    cardiovascular, renal and metabolic diseases, which we formed in 2015. 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="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 $3.4 billion, which is comprised of a $65 million upfront payment, up to $290 million in license fees, up to $865 million
    in development milestone payments and up to $2.2 billion in regulatory 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, 2023, we have received more than $300 million in payments under this
    collaboration. We will achieve the next payment of $10 million if AstraZeneca advances a medicine under this collaboration<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;">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> 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 period we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. For example, in 2023, we earned a
    $36 million payment when AstraZeneca licensed ION826 from us. We recognized this payment in full in 2023 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;">During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with AstraZeneca (in thousands, 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;">2023</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; 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;">Revenue from our relationship with AstraZeneca</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;">202,236</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;">79,160</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;">254,591</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;">26</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;">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>

  </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, 2023 and 2022.</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 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. Upon initiating the collaboration, we received an upfront payment of $35
    million. Under our collaboration, GSK is developing bepirovirsen for the treatment of chronic hepatitis B virus infection, or 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="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 and commercializes
    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, 2023, we have received more than $105 million in an upfront payment and payments related to 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;">We completed our R&amp;D services performance obligations in 2015, therefore 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 2023, we earned a $</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment when GSK initiated a Phase 3 program of
      bepirovirsen. We recognized this milestone payment as R&amp;D revenue in full in 2023 because we did not have any remaining performance obligations related to the milestone payment. 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, 2023, 2022 and 2021, we earned the following revenue from our relationship with GSK (in thousands, 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;">2023</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; 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;">Revenue from our relationship with GSK</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;">15,000</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: 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;">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;">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</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: 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, 2023 and 2022.</div>

<div><br/>
  </div>

<div style="text-align: left; 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; font-style: italic;">Pelacarsen 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;">In 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 that Novartis initiated in 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;">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. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received more than $</span>275<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration. We</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> will achieve the next payment of $</span>50<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if the FDA accepts an NDA filing 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 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>

    <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>

    <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>

    <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>

    <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>

    <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>

    <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 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>

    <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>

    <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>

    <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>

    <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>

    <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;">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 Note 7, <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 Medicine for the Treatment of Lp(a)-Driven Cardiovascular 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 August 2023, we entered into a collaboration and license agreement with Novartis for the discovery, development and commercialization
    of a novel medicine for patients with Lp(a)-driven cardiovascular disease, or CVD. Novartis is solely responsible for the development, manufacturing and potential commercialization of the next generation Lp(a) therapy.</div>

<div><br/>
  </div>

<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 $730 million, which is comprised of a $60 million upfront payment, up to $155 million in development milestone payments, up to $105
    million in regulatory milestone payments and up to $410 million in sales milestone payments. In addition, we are eligible to receive tiered
    royalties ranging from 10 percent to 20 percent
    on net sales. From inception through December 31, 2023, we have received $60 million from the upfront payment we received under this collaboration. We will achieve the next payment of $5 million if we designate a development candidate 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 Novartis. We determined the transaction price to be the $60 million upfront payment we received in the fourth quarter 2023. We allocated the transaction price 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. We currently estimate we will satisfy our performance obligation at the
    end of the research term in June 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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Novartis (in thousands, 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;">2023</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; 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;">Revenue from our relationship with Novartis</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;">30,194</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;">237</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;">25,526</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: 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;" 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;">4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less than 1%</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;">3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; 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;">Our consolidated balance sheet at December 31, 2023 included deferred revenue of $30.0 million related to our relationship with Novartis. We did not have any deferred revenue from our relationship with Novartis at December 31, 2022.</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 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 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. As a result, 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 collaboration. From inception through December 31, 2023, 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 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 period in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In 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 independent data monitoring committee, or 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 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 multiple 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 immunoglobulin A, or IgA, nephropathy, or IgAN, and one for the treatment of patients with GA, the advanced stage of dry AMD. In April 2023, Roche initiated a Phase 3 study of IONIS-FB-L<sub>Rx</sub> in patients with IgAN.</div>

<div><br/>
  </div>

<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 in patients
      with IgAN, </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;">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 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 milestone payments, up to $</span>279<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone payments 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, 2023,
    we have received more than $135 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. From inception through December 31, 2023, we have included $97 million in upfront and milestone payments in
    the transaction price for our R&amp;D services performance obligation under this collaboration, including $22 million of milestone payments we
    achieved in 2022. 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 fourth 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; font-style: italic;">RNA-Targeting Medicines for Alzheimer's Disease and Huntington'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 September 2023, we entered into an agreement with Roche to develop two undisclosed early-stage programs for RNA-targeting investigational medicines for the treatment of AD and HD. Under the agreement, we are responsible for advancing the two programs through preclinical studies and Roche is responsible for clinical development, manufacturing and commercialization of the medicines if they
    receive regulatory approval.</div>

<div><br/>
  </div>

<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 $625 million, which is comprised of a $60 million upfront payment, up to $167 million in development milestone payments and up to $398
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales. From inception through December 31, 2023, we have received $60 million from the upfront payment we received under this collaboration. We will achieve the next
    payment of $7.5 million if we advance 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;">We identified two performance
    obligations under this new agreement, comprised of R&amp;D services for each of the two separate programs. We determined the transaction price
    to be the $60 million upfront payment we received in the fourth quarter 2023. 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>

    <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;">$45 million for the R&amp;D services for the investigational
            medicine for AD; 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>

    <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>15<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the R&amp;D services for t</span>he investigational medicine for HD.</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 are recognizing revenue for our R&amp;D services performance obligations as we perform services based on our effort to satisfy our
    performance obligations relative to our total effort expected to satisfy our performance obligations. We currently estimate we will satisfy our performance obligations at the end of the research terms of March 2024 and March 2025 for the
    investigational medicines for AD and HD, 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;">During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with Roche (in thousands, 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;">2023</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; 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;">Revenue from our relationship with Roche</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;">48,838</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;">67,202</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;">17,241</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;">6</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</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>

  </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>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span>36.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>22.4<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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Otsuka</div>

<div><br/>
  </div>

<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 2023, we entered into an agreement with Otsuka Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe.
    We are responsible for the ongoing development of donidalorsen. We retained the rights to commercialize donidalorsen in the U.S. and in the rest of the world assuming regulatory approval.</div>

<div><br/>
  </div>

<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 $185 million, which is comprised of a $65 million upfront payment, up to $50 million in regulatory milestone payments and up to $70
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties ranging from 20 percent to 30 percent on net sales. From inception through December 31, 2023, we have received $65 million from the upfront payment we received under this collaboration. We will achieve the next
    payment of $15 million if the EMA accepts a MAA filing for donidalorsen in the EU 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;">We identified two performance
    obligations under this new agreement, comprised of our license of donidalorsen to Otsuka and R&amp;D services for donidalorsen. We determined the transaction price to be the $65 million upfront payment we received in the fourth quarter 2023. 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>

    <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;">$56 million for the license of donidalorsen; 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>

    <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;">$9 million for the R&amp;D services for donidalorsen.</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 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 obligations in March 2026.</div>

<div><br/>
  </div>

<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 year ended December 31, 2023, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amount):</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;" 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: 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; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <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; font-weight: bold;">2023</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: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Otsuka</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;">56,480</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: -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;">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>

  </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>2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred revenue of $</span>8.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
      million related to our relationship with Otsuka.</span></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 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 and September 2023, we started receiving
    royalties from PTC for TEGSEDI and WAYLIVRA sales, respectively<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-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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2021, we began commercializing TEGSEDI and WAYLIVRA in
      Europe and TEGSEDI in North America through distribution agreements with Sobi. </span>Under our distribution agreements, Sobi is responsible for commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. We are
    responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. Under our agreements with Sobi, Sobi does not generally have a right of return. We recognize as revenue the price Sobi
    pays us for the inventory when we deliver the finished goods inventory to Sobi. In addition, 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;">In October 2023, our distribution agreement for TEGSEDI in North America was terminated. As a result, we are currently transitioning
    responsibilities from Sobi to us in order to continue serving the impacted patient community. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In February 2024, we began the process to withdraw the TEGSEDI NDA.</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, 2023, 2022 and 2021, we earned the following revenue from our distribution agreement with Sobi for TEGSEDI in North America (in thousands, 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;">2023</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; 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;">TEGSEDI revenue from our distribution agreement with Sobi in North America</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;">2,646</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; 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;">4,004</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;">7,443</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: 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;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less than 1%</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;">1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</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;">1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; 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="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 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 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 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.</div>

<div><br/>
  </div>

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

<div><br/>
  </div>

<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 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 and will pay Metagenomi certain fees for the selection of genetic targets. 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. In addition, we will pay
    Metagenomi milestone payments and royalties that are contingent on the achievement of certain development, regulatory and sales events. We will also 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 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><br/>
  </div>

<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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Alnylam (in thousands, 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;">2023</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; 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;">Revenue from our relationship with Alnylam</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;">28,426</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;">21,389</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: 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;">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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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</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</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 Alnylam at December 31, 2023 and 2022.</div>
<span></span>
</td>
</tr>
</table>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989543266288">
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<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, 2023</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_InvestmentsAbstract', window );"><strong>Investments [Abstract]</strong></a></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5. 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, 2023:</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>
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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;">68</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;">24</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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); 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: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);" 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%; background-color: rgb(255, 255, 255); border-bottom: 4px double rgb(0, 0, 0); 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, 2023,
    92 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;">We invest in debt securities with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp;
    Poor&#8217;s, Moody&#8217;s or Fitch, 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At December 31, 2023, we had an ownership interest of less than 20 percent </span>in seven
    private companies and three public companies with which we conduct business<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;">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%;">


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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;">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, 2023</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>

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    <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;">559,967</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;">157</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;">(2,625</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;">557,499</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;">224,711</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;">64</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;">(611</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;">224,164</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;">513,784</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">
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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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">512,047</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: 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;">17,757</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;">42</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;">(113</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;">17,686</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">
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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;">1,316,219</div>
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    <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;">415</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;">(5,238</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;">1,311,396</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;">243,151</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;">1,270</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;">(692</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;">243,729</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;">110,138</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;">547</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;">(21</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;">110,664</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;">294,873</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;">1,239</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;">(480</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;">295,632</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;">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: #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;">3,466</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</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;">(4</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;">3,469</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; margin-left: 18pt; 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: #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;">651,628</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;">3,063</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;">(1,197</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;">653,494</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: 27pt; 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: #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">
          <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 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,967,847</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">
          <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 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,478</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,435</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,964,890</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;">Equity 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">&#160;</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">&#160;</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">&#160;</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">&#160;</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;">Publicly traded equity securities included in other current assets (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">
          <div style="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;">11,897</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;">236</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;">(5,832</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;">6,301</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;">Privately held securities included in deposits and other assets (3)</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;">23,115</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;">25,001</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;">(5,125</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;">42,991</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; margin-left: 18pt; 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: #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">
          <div style="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;" 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: #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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,237</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,957</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49,292</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; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; margin-left: 36pt; 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: #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">
          <div style="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: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,002,859</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">&#160;</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">
          <div style="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: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,715</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">&#160;</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">
          <div style="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: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(17,392</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>

    <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">
          <div style="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: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,014,182</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">&#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, 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">
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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>

    <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; margin-left: 18pt; 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>

    <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; margin-left: 18pt; 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; margin-left: 36pt; 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; 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;">Publicly traded 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;">Privately held 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; margin-left: 18pt; 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; margin-left: 36pt; 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 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 publicly traded equity securities are included in other current
            assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2023, we recorded a $4.2 million net <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">unrealized loss in our consolidated statements of
              operations related to changes in the fair value of our investments in publicly traded companies.</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;">(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 privately held equity securities are included in deposits and other assets. We recognize our privately held 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, which are Level 3 inputs. In the year ended December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recorded a $</span>2.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million net unrealized gain in our consolidated statements of operations related to changes in the fair value of our investments in privately held companies.</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, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;(in thousands, except for number of investments):</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; white-space: nowrap;" 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; white-space: nowrap;" 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;">297</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;">323,708</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;">(553</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;">178,183</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;">(2,764</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;">501,891</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;">(3,317</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;">63</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;">199,372</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;">(246</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;">14,777</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%; 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;">(386</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;">214,149</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;">(632</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;">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; 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;">325,966</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;">(1,031</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;">131,000</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;">(1,338</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;">456,966</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;">(2,369</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%; 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;">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; 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;">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>

    <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;">8,352</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; 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;">(17</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; 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;">7,888</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; 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;">(100</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; 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;">16,240</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; 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;">(117</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: 16%; padding-bottom: 4px; 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;">Total temporarily impaired securities</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%; border-bottom: #000000 double 4px; 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 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">455</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; 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;">857,398</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; 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;">(1,847</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; 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;">331,848</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; 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;">(4,588</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; 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;">1,189,246</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; 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;">(6,435</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">
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates
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<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. Fair Value Measurements</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 following tables present the major security types we held at December 31, 2023 and 2022&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. 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
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<div><br/>
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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </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, 2023</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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" 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>
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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; 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;">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>

  </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;">Cash equivalents (1)</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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">185,424</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;">185,424</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">
          <div style="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 (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;">801,228</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;">801,228</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 (3)</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;">334,828</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;">334,828</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 (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;">807,679</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;">807,679</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 (3)</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;">21,155</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;">21,155</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>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (5)</div>
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        </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;">6,301</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;">6,301</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: 4px; background-color: #CCEEFF;" 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; 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;">2,156,615</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">&#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;">999,404</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;">1,157,211</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">&#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; white-space: nowrap;" 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, 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; white-space: nowrap;" 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; white-space: nowrap;" 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>

  </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;">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 (4)</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 (3)</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 (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;">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 (3)</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 (3)</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 (5)</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 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;">$33.0 million was included in cash and cash equivalents, 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;">(3)</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 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;">$11.0 million was included in cash and cash equivalents, 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;">(5)</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>

<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 1.75% Notes, 0% Notes and 0.125% Notes had a fair value of $661.1 million, $667.8 million and $42.4 million at December 31, 2023,
    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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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for the fair value of financial instruments (as defined), including financial assets and financial liabilities (collectively, as defined), and the measurements of those instruments as well as disclosures related to the fair value of non-financial assets and liabilities. Such disclosures about the financial instruments, assets, and liabilities would include: (1) the fair value of the required items together with their carrying amounts (as appropriate); (2) for items for which it is not practicable to estimate fair value, disclosure would include: (a) information pertinent to estimating fair value (including, carrying amount, effective interest rate, and maturity, and (b) the reasons why it is not practicable to estimate fair value; (3) significant concentrations of credit risk including: (a) information about the activity, region, or economic characteristics identifying a concentration, (b) the maximum amount of loss the entity is exposed to based on the gross fair value of the related item, (c) policy for requiring collateral or other security and information as to accessing such collateral or security, and (d) the nature and brief description of such collateral or security; (4) quantitative information about market risks and how such risks are managed; (5) for items measured on both a recurring and nonrecurring basis information regarding the inputs used to develop the fair value measurement; and (6) for items presented in the financial statement for which fair value measurement is elected: (a) information necessary to understand the reasons for the election, (b) discussion of the effect of fair value changes on earnings, (c) a description of [similar groups] items for which the election is made and the relation thereof to the balance sheet, the aggregate carrying value of items included in the balance sheet that are not eligible for the election; (7) all other required (as defined) and desired information.</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> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482106/820-10-50-2<br></p></div>
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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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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Long-Term Obligations and Commitments</div>

<div><br/>
  </div>

<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>
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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;">2023</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>

  </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;">1.75</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;">562,285</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: 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</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;">625,380</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;">622,242</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;"><span style="text-indent: 0pt;">0.125</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">&#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;">544,504</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;">Liability related to sale of future royalties</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;">513,736</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;">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;">178,969</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;">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>

  </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;">8,859</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;">8,998</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;">33,714</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;">7,295</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>

  </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;">1,922,943</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;">1,369,195</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;">(8,831</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;">(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>

  </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;">1,914,112</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;">1,361,660</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </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 of December 31, 2023, our 0.125%
    Notes was classified as a current liability because it matures in December 2024.</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;">1.75%
    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 2023, we completed a $575.0
    million offering of convertible senior notes and used $488.2 million of the net proceeds from the issuance of the 1.75% Notes to repurchase $504.4 million in
    principal of our 0.125% Notes. We expect to use the remaining net proceeds to settle the 0.125% Notes that remain outstanding.</div>

<div><br/>
  </div>

<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, 2023, we had the following 1.75%
    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"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" 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;">1.75% 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;">575.0</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: 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;">12.7</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_6bfb094eab7041389566a848570cbbe5">June 2028</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; width: 88%;" 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; 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;">1.75</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: top; width: 88%; 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; 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;">2.3</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: 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;">53.73</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;">Total shares of common stock subject to conversion</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;">10.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </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;">0%
    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 2021, we completed a $632.5
    million offering of convertible senior notes. We used $319.0 million of the net proceeds from the issuance of the 0% Notes to pay the remaining $309.9 million
    principal balance of our 1% Notes 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;">At December 31, 2023, 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"> </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;">7.2</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: 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_77100aa329424b42b6f03dc4fa1e2472">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; width: 88%;" 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; 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;">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: top; width: 88%; 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; 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;">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: 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 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 <span style="-sec-ix-hidden:Fact_c2c8af8268614a7d9201a587fc5822f5">April 2026</span>. The note hedges and warrants are separate transactions and are not part of the terms of our&#160; 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 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%
    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 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of
    our 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;">As discussed above, in 2023, we repurchased $504.4
    million of our 0.125% Notes. We are holding the repurchased 0.125% Notes in treasury until maturity. As a result, the remaining principal balance of our 0.125%
    Notes was $44.5 million as of December 31, 2023.
    Additionally, during the year ended December 31, 2023, we recorded a $13.4 million gain on the early retirement of debt, which we recorded as other income in our consolidated statements of operations. The gain on the early retirement of our debt is the difference
    between the amounts paid to repurchase our 0.125% Notes and the net carrying balance of the liability at the time that we completed the
    repurchases.</div>

<div><br/>
  </div>

<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, 2023, 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"> </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;">44.5</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;">0.2</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: 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_5c75d58f5a434990850c3cf960d7b0c3">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; width: 88%;" 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; 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;">0.125</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: top; width: 88%; 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; 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;">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: 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, excluding shares related to <span style="text-indent: 0pt;">0.125</span>% Notes we have repurchased and are currently holding in treasury</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;">0.5</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 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 </span><span style="-sec-ix-hidden:Fact_b2783015cbc64323aab97584a4bd55af">December 2024</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. 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><br/>
  </div>

<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 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;">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 1.75%, 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.</div>

<div><br/>
  </div>

<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, 2023, 2022 and 2021 included $5.9 million, $5.3 million and $4.9 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 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 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 2022, we concurrently entered into two
    purchase and sale agreements with a real estate investor. In the same period, we closed the first transaction in which we sold the facilities at our headquarters in Carlsbad, California, which includes our primary R&amp;D facility, for a purchase price
    of $263.4 million. As a result, 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 in our consolidated statements of operations. 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. In connection with this transaction, we leased back
    our headquarters facilities for an initial lease term of 15 years with options to extend the lease for two additional terms of five years each.</div>

<div><br/>
  </div>

<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 August 2023, we closed the second transaction and transferred legal ownership of two lots of undeveloped land adjacent to our headquarters to the real estate investor for a purchase price of $33 million. In connection with this transaction, we entered 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 R&amp;D and office 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 15 years with options to extend the lease for two additional terms of five years each. The lease will commence once the structure of this new facility is completed.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Since the building is under construction and unavailable to lease, we are unable to complete the sale-leaseback evaluation under ASC 842,
    Leases. As a result, the land remains in our consolidated balance sheets and we accounted for the proceeds as a financial liability. We will reassess the transaction under the sale-leaseback accounting guidance when the facilities are available for
    lease commencement.</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, 2023 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;">2024</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;">55,298</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;">2025</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;">10,657</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;">2026</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;">643,157</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;">2027</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;">10,509</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;">2028</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;">580,277</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;">8,462</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;">1,308,360</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: 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;">(157</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;">(47,138</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;">(20,061</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 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;">1,241,004</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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> <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. 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.</div>

<div><br/>
  </div>

<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 upfront payment of $500
    million as a liability related to the sale of future royalties, net of transaction costs of $10.4 million, which we are amortizing over the
    estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty
    Pharma as a reduction of the liability.</div>

<div><br/>
  </div>

<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 determine the effective interest rate used to record
      interest expense under this agreement based on an estimate of future royalty payments to Royalty Pharma. As of </span>December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the estimated effective interest rate under the agreement was </span>13.5 percent<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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our liability related to
      sale of future royalties for the year ended </span>December 31, 2023<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: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of future royalties</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;">500,000</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;">Royalty payments to Royalty Pharma</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;">(44,628</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: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</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;">68,238</div>
        </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>

  </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;">Liability related to sale of future royalties as of December 31, 2023</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;">523,610</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance costs related to sale of future royalties</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;">(10,434</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: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties as of December 31, 2023</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;">560</div>
        </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>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of December 31, 2023</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;">513,736</div>
        </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">&#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;">There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty
    payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the commercial sales of SPINRAZA, the regulatory approval and commercial sales of
    pelacarsen, competing products or other significant events.</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 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 an additional office space and warehouse space in Carlsbad. We lease these spaces under non-cancelable operating leases. In
    2022, we exercised our option to extend the office space lease, extending our term from January 2023 to May 2027. We have no remaining options
    to extend this lease. Our warehouse space lease in Carlsbad has an initial term ending in 2028 with no options to extend the 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;">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 2022. 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. 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
    transfer of legal ownership of the two lots of undeveloped land to the real estate investor, we entered 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. The lease will commence once the structure of this new facility is completed.</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 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility to be constructed by
    the lessor in Oceanside, California. We capitalized costs that we incurred related to the design and development of tenant improvements as construction-in-progress in our consolidated balance sheets. In August 2023, we reached a mutual agreement with
    the lessor to terminate the lease agreement. As a result, we recorded a charge of $20 million, primarily associated with the impairment of
    construction-in-progress assets, within <span style="-sec-ix-hidden:Fact_ebdf1ed5cf6845079198439e7c520f42">SG&amp;A expense</span> 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; 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 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 in January 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 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 in November 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; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At December 31, 2023</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;">171.9</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: 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;">179.0</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;">13.0 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>
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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;">During the years ended December 31, 2023,
    2022, and 2021 we paid $20.1 million, $4.0 million and $3.3 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, 2023,
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<div><br/>
  </div>

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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </td>

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          <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>
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          <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>

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          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2024</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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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,398</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>

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          <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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">20,645</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;">2026</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;">20,781</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>

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          <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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">20,800</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;">2028</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;">20,774</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>

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          <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;">176,138</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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  <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;">279,536</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: 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;">(100,567</div>
        </td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

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          <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>
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    <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;">(8,094</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>

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          <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;">170,875</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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<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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<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 $23.1 million,
    $8.3 million and $3.4 million for the
    years ended December 31, 2023, 2022
    and 2021, respectively. </div>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989633188896">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity<br></strong></div></th>
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<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;">8. Stockholders</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> Equity</span></div>

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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Preferred Stock</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 are authorized to issue up to 15
    million shares of &#8220;blank check&#8221; Preferred Stock. As of December 31, 2023, 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, 2023.</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, 2023 and 2022, we had 300 million shares of common
    stock authorized, of which 144.3 million and 142.1 million were issued and outstanding, respectively. As of December 31, 2023,
    total common shares reserved for future issuance were 49.7 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, 2023,
    2022 and 2021, we issued 2.3 million, 1.2 million and 1.1 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 $49.4 million, $6.4
    million and $11.6 million in 2023,
    2022 and 2021, respectively.</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 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 Stock Option Plan, or 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 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. At December 31, 2023, no options were outstanding and 68,000 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 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 June 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>In June 2023, after receiving approval from our stockholders, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2011 Plan to increase the total number of shares of common stock
      authorized for issuance under the 2011 Plan from </span>29.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
      million to </span>35.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million.</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 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, 2023, a total of 12.8 million
    options were outstanding, of which 8.7 million were exercisable, 3.3 million restricted stock unit awards were outstanding, and 8.0 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 2020, we assumed the
      unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In 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, 2023, a total of 0.4 million
    options were outstanding, of which 0.1 million were exercisable, 0.2 million restricted stock unit awards were outstanding, and 1.0 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>

    <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>

    <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>

    <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>

    <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>

    <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>

    <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>

<div><br/>
  </div>

<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 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 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 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>

<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;"><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>

  </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>

    <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>

<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>

    <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>

<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>

    <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>

<div><br/>
  </div>

<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 10 years
    from the date of grant. At December 31, 2023, a total of 0.9 million options were outstanding, of which 0.9 million were exercisable, 40,000 restricted stock unit awards were outstanding, and 0.5
    million shares were available for future grant under the 2002 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;">Employee Stock Purchase 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 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, 2023. The ESPP
    permits full-time employees to purchase common stock through payroll deductions (which cannot exceed 10 percent of each employee&#8217;s compensation)
    at the lower of 85 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 six months from the date of purchase. During 2023, employees purchased and we issued to employees 0.1
    million shares under the ESPP at a weighted average price of $30.53 per share. At December 31, 2023, there were 0.4 million shares available for purchase under the
    ESPP.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock Option 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 stock option activity under our stock plans for the year ended December 31, 2023 (in thousands, except per share and contractual life 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; white-space: nowrap;" 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; white-space: nowrap;" 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; white-space: nowrap;" 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; white-space: nowrap;" 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, 2022</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">
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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>
        </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;">50.57</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;">2,407</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;">38.80</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;">(1,444</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;">45.06</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;">(1,842</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;">55.90</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, 2023</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;">14,091</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;">48.43</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;">4.74</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;">78,542</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, 2023</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;">9,703</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;">52.24</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;">3.20</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;">28,349</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 $19.72, $18.66 and $24.35 for the years ended December 31, 2023, 2022 and 2021, respectively. The total intrinsic value of options
    exercised during the years ended December 31, 2023, 2022 and 2021 were $6.0 million, $1.4 million and $2.5 million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $65.1 million, $3.6 million and $8.5 million for the years ended December 31, 2023, 2022 and 2021, respectively. For the year
    ended December 31, 2023, the weighted-average fair value of options exercised was $49.23. As of December 31, 2023, total unrecognized compensation cost related to
    non-vested stock options was $36.6 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, 2023 (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; white-space: nowrap;" 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, 2022</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;">2,766</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;">48.30</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;">1,707</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;">40.51</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;">(1,055</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;">51.64</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;">(179</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;">42.90</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, 2023</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;">3,239</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;">43.40</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, 2023,
    2022 and 2021, the
    weighted-average grant date fair value of RSUs granted was $40.51, $36.14 and $57.02 per RSU, respectively. As of December 31, 2023, total unrecognized compensation cost related to RSUs was $53.7 million. We expect to recognize this cost over a weighted average period of 1.3
    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, 2023 (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; white-space: nowrap;" 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, 2022</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;">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">
          <div style="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;">52.59</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: 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;">158</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;">57.43</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</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;">(75</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%; padding-bottom: 2px; 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: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.43</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; 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, 2023</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;">226</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;">56.04</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;">For the years ended December 31, 2023,
    2022 and 2021, the
    weighted-average grant date fair value of PRSUs granted was $57.43, $42.28 and $77.17 per PRSU, respectively. As of December 31, 2023, total unrecognized compensation cost related to PRSUs was $4.4 million. We expect to recognize this cost over a weighted average period of 1.4
    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, 2023, 2022 and 2021 (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;">2023</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; 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;">499</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;">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>

  </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;">77,826</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;">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>

  </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;">27,484</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;">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>

  </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;">105,809</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;">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>

  </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;">Refer to 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, 2023,
    2022 and 2021, 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;">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;">2023</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; 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;">3.8</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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>

  </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;">46.8</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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>

  </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;">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>

  </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;">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;">2023</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; 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;">3.8</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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>

  </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;">52.7</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;">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>

  </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;">7.7 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>

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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: 12pt;"><br/>
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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;">ESPP:</div>

<div><br/>
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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>

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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>

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        </td>

  </tr>

  <tr>

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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>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
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        </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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          <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%;" valign="bottom">&#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;">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>

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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>

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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">&#160;</td>

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    <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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          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div>
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          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div>
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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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<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;"><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
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<div><br/>
  </div>

<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 years ended December 31, 2023 and 2022. Under the simplified method, we
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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;"><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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<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>The entire disclosure for equity.</p></div>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989633163056">
<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>
</tr>
<tr><th class="th"><div>Dec. 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_us-gaap_IncomeTaxDisclosureAbstract', window );"><strong>Income Taxes [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_IncomeTaxDisclosureTextBlock', 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;">9. Income Taxes</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;">Loss before income taxes is comprised of (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;">2023</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; 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;">(334,707</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;">(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>

  </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;">742</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;">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>

  </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;">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;">(333,965</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;">(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>

  </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;">Our income tax expense (benefit) 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="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;">2023</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;" 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;">35,861</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;">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>

  </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;">(3,687</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;">1,129</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>

  </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;">147</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;">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>

  </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">
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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;">11,737</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;">(551</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">&#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;">&#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%; 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;">&#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: -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;">32,321</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;">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>

  </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;">Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to loss before income 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;">2023</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;">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>

  </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;">Pre-tax loss</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;">(333,965</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;">(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>

  </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;">(70,133</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>

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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">
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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>

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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">
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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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        </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">
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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>

    <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">
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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">
          <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">
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        </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>

    <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;">(22</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;">(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>

  </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;">175,388</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;">(52.5</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9.9</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>

  <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;">Loss on debt transactions</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;">&#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;">262</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;">(0.9</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; 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;">Tax credits</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;">(67,131</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;">20.1</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">(39,729</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;">15.4</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">(23,198</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>

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  </tr>

  <tr>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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">
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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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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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">
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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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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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>
        </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">
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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;">(1.1</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">
          <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">&#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>
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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">
          <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;">327</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;">(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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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">
          <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;">84</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>

    <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;">Foreign-derived intangible income benefit</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;">(7,493</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;">2.2</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;">&#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">&#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;">&#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">&#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>
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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">
          <div style="text-align: left; 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;">19,546</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;">(5.9</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;">14,030</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;">(5.4</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;">4,720</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;">(16.2</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>

  </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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(405</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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); 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: 4px double rgb(0, 0, 0);" valign="bottom">
          <div style="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: 4px double rgb(0, 0, 0);" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,321</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: 4px double rgb(0, 0, 0);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); white-space: 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: 4px double rgb(0, 0, 0);" valign="bottom">
          <div style="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: 4px double rgb(0, 0, 0);" 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: 4px double rgb(0, 0, 0);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" 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%; border-bottom: 4px double rgb(0, 0, 0); white-space: 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: 4px double rgb(0, 0, 0);" valign="bottom">
          <div style="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: 4px double rgb(0, 0, 0);" 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: 4px double rgb(0, 0, 0);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" 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%; border-bottom: 4px double rgb(0, 0, 0); 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, 2023 and 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; 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;">2023</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>

  </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>

  </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 operating loss carryovers</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;">77,964</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;">87,802</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;">Tax credits</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;">239,962</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;">277,436</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;">71,683</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;">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>

  </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;">77,468</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;">86,983</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;">104,380</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;">104,649</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </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;">16,849</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;">34,384</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;">Capitalized research and development 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;">238,738</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;">119,635</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;">Long-term 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">&#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;">43,718</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;">45,612</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sale of future royalties</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;">144,608</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: 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;">10,343</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;">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>

  </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;">1,025,713</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;">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>

  </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;">(4,166</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;">(4,475</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>

  </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;">(42,007</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;">(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>

  </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;">(1,910</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;">(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>

  </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;">977,630</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;">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>

  </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;">(977,630</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;">(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>

  </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 $169
    million from December 31, 2022 to December 31, 2023.
    The increase was primarily related to increases in our deferred tax assets for capitalized research and development expenses and sale of future 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;">At December 31, 2023, we had
    federal and state, primarily California, tax net operating loss carryforwards of $242.8 million and $398.8 million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2032. At December 31, 2023, we also had federal and California research and development tax credit carryforwards of $169.7 million and $124.4 million, respectively. Our federal research and development
    tax credit carryforwards will begin to expire in 2038. Our California research and development tax credit carryforwards are available indefinitely. Our 2023 current tax expense includes a benefit of approximately $3.2 million related to utilization of state tax loss carryforwards, primarily California.</div>

<div><br/>
  </div>

<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;">2023</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; 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;">56,567</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;">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>

  </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 lapse of statute of limitations</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;">(14,993</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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: 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%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">(737</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;">(267</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;">(695</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;">Increase 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;">429</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;">259</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;">263</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;">Increase for current period tax positions</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;">2,032</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;">1,490</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;">1,354</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;">Ending balance of unrecognized tax benefits</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;">43,298</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;">56,567</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;">55,085</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;">Included in the balance of unrecognized tax benefits at December 31, 2023, 2022 and 2021 was $0.3 million, $6.2 million and $6.2 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 $7.6 million within the next 12 months due to the lapse of statute of limitations on underlying tax positions primarily related to amortization of certain
    capitalized state research and development expenditures.</div>

<div><br/>
  </div>

<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, 2023, 2022 and 2021, we recognized $0.1 million, $0.8 million and $0.5 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are subject to taxation in the U.S. and various state and
      foreign jurisdictions. U.S. tax years 2020 through 2022 remain open to examination and tax years 2019 through 2022 remain open to examination by major state taxing jurisdictions, primarily California, although net operating loss and credit
      carryforwards generated prior to these periods 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</span>.</div>
<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for income taxes. Disclosures may include net deferred tax liability or asset recognized in an enterprise's statement of financial position, net change during the year in the total valuation allowance, approximate tax effect of each type of temporary difference and carryforward that gives rise to a significant portion of deferred tax liabilities and deferred tax assets, utilization of a tax carryback, and tax uncertainties information.</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> -Topic 946<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 13<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480990/946-20-50-13<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org//740/tableOfContent<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 14<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-14<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 21<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-21<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 270<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482526/740-270-50-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 17<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-17<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.5.Q1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 11.C)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-2<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482603/740-30-50-2<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">
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989542765120">
<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>
</tr>
<tr><th class="th"><div>Dec. 31, 2023</div></th></tr>
<tr class="re">
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<td class="text">&#160;<span></span>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">10. Employment Benefits</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;">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 $22,500 and $30,000 in 2023 for employees under 50 years old and employees 50 years old or over,
    respectively. We made approximately $7.1 million, $5.6
    million and $5.5 million in matching contributions for the years ended December 31, 2023, 2022 and 2021, respectively.</div>
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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>The entire disclosure for retirement benefits.</p></div>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989545249200">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Legal Proceedings<br></strong></div></th>
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<tr><th class="th"><div>Dec. 31, 2023</div></th></tr>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">11. Legal Proceedings</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;">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
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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;">There are no pending material legal proceedings to which we are a party or of which our property is the subject.</div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for legal proceedings, legal contingencies, litigation, regulatory and environmental matters and other contingencies.</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> -Topic 450<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org//450/tableOfContent<br></p></div>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989539348240">
<tr>
<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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<tr><th class="th"><div>Dec. 31, 2023</div></th></tr>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">12. Fourth Quarter Financial Data (Unaudited)</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 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 2023 and 2022 are as follows (in thousands, except per share 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;">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;">Revenue (1)</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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">324,505</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;">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>

  </tr>

  <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;">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;">330,627</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;">359,909</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;">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;">(6,122</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;">(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>

  </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 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;">(9,263</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;">(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>

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  <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 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;">(0.06</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;">(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>

  </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 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;">(0.06</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;">(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>

  </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 higher in the three months ended December 31, 2023
            compared to the same period in 2022 primarily due to the $50 million milestone payment we earned from AstraZeneca when the FDA approved
            WAINUA for ATTRv-PN in the U.S., $36 million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth
            quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis.</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 lower in the three months ended December 31,
            2023 compared to the same period in 2022 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>

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    <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>

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  <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 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>

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          <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 loss per share by dividing the total net loss by our weighted-average number of common shares outstanding
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        </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: 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 incurred a net loss for the fourth quarter of 2023 and 2022. As a
            result, 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.</div>
        </td>

  </tr>


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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Insider Trading Arrangements<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr>
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<div>Dec. 31, 2023 </div>
<div>shares</div>
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<div>Dec. 31, 2023 </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 quarter ended December 31, 2023, our
    officers and directors (as defined in Rule 16a-1(f) under the Exchange Act), or Section 16 officers and directors, adopted or terminated contracts, instructions or written plans for the purchase or sale of our securities as noted in the table below.</div>

<div><br/>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8220;Non-Rule 10b5-1 trading arrangement&#8221; as defined in item 408(c) of Regulation S-K under the Exchange Act.</div>
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  </tr>


</table>

<div><br/>
  </div>

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    <td rowspan="2" style="width: 2.45%; vertical-align: bottom;">&#160;</td>

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    <td rowspan="2" style="width: 2.14%; vertical-align: 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;">Date</div>
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    <td rowspan="2" style="width: 2.26%; vertical-align: bottom;">&#160;</td>

    <td colspan="3" style="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;">Trading Arrangement</div>
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    <td rowspan="2" style="width: 2.14%; vertical-align: 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;">Total Shares</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Rule 10b5-1*</div>
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    <td style="width: 2.26%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_9190fcfa2d974e0a83a1d614c438f473">February 28, 2025</span></div>
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  </tr>


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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_ecd_TrdArrIndName', window );">Name</a></td>
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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_ecd_TrdArrIndTitle', window );">Title</a></td>
<td class="text">Board Member<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_ecd_TrdArrAdoptionDate', window );">Adoption Date</a></td>
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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_ecd_TrdArrDuration', window );">Arrangement Duration</a></td>
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<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 Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 1<br></p></div>
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<td><strong> Name:</strong></td>
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<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 Regulation S-K<br> -Number 229<br> -Section 408<br> -Subsection a<br> -Paragraph 2<br> -Subparagraph B<br></p></div>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538778784">
<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, 2023</div></th></tr>
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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_ConsolidationPolicyTextBlock', window );">Basis of Presentation</a></td>
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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>

<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;">In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;).</div>
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<tr class="re">
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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>

<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 prepare our consolidated financial statements in conformity with accounting principles generally accepted in the United States, or
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<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_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
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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;">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 WAINUA 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 selling, general and administrative, or SG&amp;A, expense and research and development, or R&amp;D, 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>

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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;">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>

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</table>

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  </div>

<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>

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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 and our partner approved the contract and we are both committed to perform our obligations;</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;">We have identified our rights, our partner&#8217;s rights and the payment terms;</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 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>

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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;">We believe collectability of the consideration is probable.</div>
        </td>

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</table>

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  </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>

    <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>

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</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>

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  </div>

<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 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. When a partner exercises its option to license a
      medicine that was not previously determined to be a material right at the inception of the agreement 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.</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;">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>

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</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 that 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>

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    <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>

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</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>

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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>

  </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 expenses we may incur;</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 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>

  </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 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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    <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 number of internal hours we will spend performing these services;</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;">The estimated cost of work we will perform;</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;">The estimated cost of work that we will contract with third parties to perform; 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;">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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    <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;">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;">We recognize royalty revenue 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.</div>

<div><br/>
  </div>

<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 Swedish Orphan Biovitrum AB, or 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; 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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    <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>

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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;">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>

    <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>

<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>

    <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>

<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>

    <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 Note 4, <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>
<span></span>
</td>
</tr>
<tr class="re">
<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, 2023,
    approximately 87.8 percent of our contracts receivables were from one significant customer. As of December 31, 2022, approximately 82.5 percent of our contracts receivables were from one
    significant customer.</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, 2023 and 2022, we recognized $78.2 million and $73.5 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 R&amp;D operations. We expense R&amp;D costs as we incur them. When we make payments for R&amp;D 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 R&amp;D expenses are costs associated with our partner agreements. In 2023, 2022 and 2021, patent expenses were $4.3 million, $4.7 million and $5.3 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>
<span></span>
</td>
</tr>
<tr class="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 our net loss by our weighted-average number of common shares outstanding during the
    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;">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, 2023,
    2022 and 2021, 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 from the following would have had an anti-dilutive effect on net loss
    per share:</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;">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;</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>

    <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>

<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>

    <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>

    <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>

    <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>

    <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>

    <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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  <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;">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 year ended December 31, 2023, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, would also have had an
    anti-dilutive effect on 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;">Additionally as of December 31, 2023, 2022 and 2021, we had warrants related to our 0% Notes and 0.125% 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 years ended
    December 31, 2023 and 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; 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 we 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 PRSUs we granted in 2020 through 2022, <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. These PRSU awards also included an alternative three-year payout mechanism, or the Alternative Calculation, under
    which we must calculate an alternative payout at the end of the final three-year measurement period assuming the only measurement period for all
    shares under the award was the three-year period. If the Alternative Calculation is greater than payouts under the sum of the three years, then such PRSU award will pay out to achieve the number of shares payable under the Alternative Calculation.</div>

<div><br/>
  </div>

<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 PRSUs we granted in 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period
    based on our relative TSR as compared to a peer group of companies and as measured at the end of the 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 200 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 Note 8, <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_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>

<div><br/>
  </div>

<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>
<span></span>
</td>
</tr>
<tr class="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 public and private biotechnology companies that we received as part
      of a technology license or partner agreement. At December 31, 2023, we held equity investments in three publicly traded companies and seven 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 publicly traded companies at their listed stock price. 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>
<span></span>
</td>
</tr>
<tr class="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 we determine as the following (in years):</div>

<div><br/>
  </div>

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


  <tr>

    <td style="width: 80.34%; vertical-align: bottom;"> </td>

    <td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Useful Lives</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; 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;">Computer software, laboratory, manufacturing and other equipment</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3 to 10</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15 to 40</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; 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;">Land improvements</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;">
          <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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 15</div>
        </td>

  </tr>

  <tr>

    <td style="width: 80.34%; 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;">Furniture and fixtures</div>
        </td>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 10</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;">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_AccruedLiabilitiesPolicyPolicyTextBlock', window );">Accrued Liabilities</a></td>
<td class="text">
<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;">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, 2023, we
    had three outstanding convertible senior notes, our 1.75% Notes, which mature in June 2028, our 0% Notes, which mature in April 2026, and
    our 0.125% Notes, which mature in December 2024. Refer to Note 7, <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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock', window );">Liability Related to Sale of Future Royalties</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Liability Related to Sale of Future 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;">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 arrangements with Biogen and Novartis, respectively. Refer to Note 7, <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 the 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;">Under our agreement with Royalty Pharma, we record upfront payments and milestone payments we receive from the sale of future royalties as
    a liability, net of transaction costs. We record royalty payments made to Royalty Pharma as a reduction of the liability or accrued interest and amortize the transaction costs over the estimated life of the royalty stream. We account for the associated
    interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the related product and recognizes the related 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 calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense using our
    current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material
    change in our estimate, we will prospectively adjust the effective interest rate and the related interest 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_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="re">
<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>

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  </div>

<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 operate 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.</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_NewAccountingPronouncementsPolicyPolicyTextBlock', window );">Recently Issued 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 Issued Accounting Standards</div>

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  </div>

<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 2023, the Financial Accounting Standards Board, or FASB, issued updated guidance on segment reporting. The guidance requires
    public companies with a single reportable segment to provide all disclosures required under ASC 280, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Segment Reporting</span>. In addition, the guidance
    requires public companies to include in interim reports all disclosures related to a reportable segment's profit or loss and assets that are currently required in annual reports. This update is effective for annual periods beginning after December 15,
    2023 and interim periods beginning after December 15, 2024. The guidance is applied on a retrospective basis for all periods presented in the financial statements, unless it is impracticable. Early adoption of this guidance is permitted. We currently
    plan to adopt the annual reporting requirements in our 2024 Annual Report on Form 10-K. We plan to adopt the interim reporting requirements in our Quarterly Report on Form 10-Q in the first quarter of 2025.</div>

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  </div>

<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 2023, the FASB issued updated guidance on income tax disclosures. The new guidance requires companies to provide additional
    disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions and unrecognized deferred tax
    liabilities. This update is effective for annual periods beginning after December 15, 2024. Early adoption of this guidance is permitted. We currently plan to adopt this guidance in our 2025 Annual Report on Form 10-K.</div>

<div><br/>
  </div>

<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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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for estimating accrued liabilities, including the liability for preclinical and 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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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for credit risk.</p></div>
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<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>
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<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> -Name Accounting Standards Codification<br> -Topic 705<br> -Publisher FASB<br> -URI https://asc.fasb.org//705/tableOfContent<br></p></div>
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<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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481544/470-10-50-1<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 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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 815<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480434/815-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(n))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480434/815-10-50-1A<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480434/815-10-50-1<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480434/815-10-50-4<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480434/815-10-50-7<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 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>
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<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>
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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> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(h)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479886/946-10-S99-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 17<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-17<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-9<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482525/740-10-45-25<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482525/740-10-45-28<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 19<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-19<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482765/220-10-50-1<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
</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 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483489/210-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483426/235-10-50-4<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 912<br> -SubTopic 330<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482105/912-330-50-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 330<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org//330/tableOfContent<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 330<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483080/330-10-50-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 330<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483080/330-10-50-4<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 6<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 270<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482989/270-10-45-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
<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/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(3)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(d))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479886/946-10-S99-3<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(f)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479886/946-10-S99-3<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(f)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479886/946-10-S99-3<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(f)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479886/946-10-S99-3<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 320<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 12<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480032/946-320-S99-12<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 320<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 19<br> -Subparagraph (2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480032/946-320-S99-19<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
</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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<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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-1<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;">us-gaap_LesseeLeasesPolicyTextBlock</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>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</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_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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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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</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://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 360<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482099/360-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -SubTopic 360<br> -Topic 958<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480321/958-360-50-6<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -SubTopic 360<br> -Topic 958<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480321/958-360-50-1<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;">us-gaap_PropertyPlantAndEquipmentPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</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_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> -Topic 310<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481569/310-20-50-4<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 310<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481569/310-20-50-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 310<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481962/310-10-50-2<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 310<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481569/310-20-50-2<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;">us-gaap_ReceivablesPolicyTextBlock</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>
<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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 730<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 05<br> -Paragraph 1<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483044/730-10-05-1<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;">us-gaap_ResearchAndDevelopmentExpensePolicy</td>
</tr>
<tr>
<td 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>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_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>
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<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>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for segment reporting.</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>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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(v)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.C.Q3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479830/718-10-S99-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.D.1.Q5)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479830/718-10-S99-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.D.3.Q2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479830/718-10-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.D.2.Q6)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479830/718-10-S99-1<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org//718/tableOfContent<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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>
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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> -Topic 310<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org//310/tableOfContent<br></p></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>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989542801056">
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<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>
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<tr><th class="th"><div>Dec. 31, 2023</div></th></tr>
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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 estimated useful life,
    which we determine as the following (in years):</div>

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

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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>

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  <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>

    <td colspan="1" style="vertical-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%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
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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;">154</div>
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    <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;">164</div>
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    <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>

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  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom">
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    <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">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
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    <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>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</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_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;">Our property, plant and equipment consisted of the following (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 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;">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;">2023</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>

  </tr>

  <tr>

    <td style="background-color: #CCEEFF; vertical-align: bottom; white-space: nowrap; width: 76%;">
          <div style="text-align: left; margin-left: 6.6pt; 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; width: 1%; 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;">79,885</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;">74,351</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: -2.4pt; 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; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">41,228</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;">41,158</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: -2.4pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leasehold 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;">28,276</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;">28,357</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: -2.4pt; 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; 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;">9,844</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;">9,575</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">&#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;">159,233</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">153,441</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: -2.4pt; 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;" 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;">(96,759</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;">(87,716</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">&#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;">62,474</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;">65,725</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: -2.4pt; 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;" 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;">8,569</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;">8,569</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; margin-left: 33.6pt; 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; 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;">71,043</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;">74,294</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_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%;">


  <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;">2023</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>

  </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;">105,967</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;">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>

  </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;">7,454</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;">7,945</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;">4,875</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;">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>

  </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;">29,598</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;">12,198</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </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;">147,894</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;">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>

  </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_ions_SupplementalFinancialDataAbstract">
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<tr><td><div class="body" style="padding: 2px;">
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<tr>
<td><strong> Name:</strong></td>
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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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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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>

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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="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>

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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>

    <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">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" 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; background-color: #CCEEFF;" valign="bottom">
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    <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">
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    <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>

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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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    <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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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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>

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  <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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">352,657</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;">207,222</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">&#160;</td>

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    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
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    <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;">126,399</div>
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    <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;">76,787</div>
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    <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>
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    <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>

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    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
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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;">479,056</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;">284,009</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;">468,061</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">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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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;">787,647</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">&#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">
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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">&#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">
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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;">810,456</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">&#160;</td>

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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, 2023</div></th></tr>
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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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts):</div>

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

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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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">428,784</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: 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;">44</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;">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>

  </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_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, 2023, 2022 and 2021, we earned the following revenue from our relationship with AstraZeneca (in thousands, 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;">2023</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; 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;">Revenue from our relationship with AstraZeneca</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;">202,236</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;">79,160</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;">254,591</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;">26</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;">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>

  </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, 2023, 2022 and 2021, we earned the following revenue from our relationship with GSK (in thousands, 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;">2023</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; 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;">Revenue from our relationship with GSK</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;">15,000</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: 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;">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;">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</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_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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Novartis (in thousands, 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;">2023</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; 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;">Revenue from our relationship with Novartis</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;">30,194</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;">237</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;">25,526</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: 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;" 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;">4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less than 1%</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;">3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; 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_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [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 year ended December 31, 2023, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amount):</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;" 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: 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; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <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; font-weight: bold;">2023</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: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue from our relationship with Otsuka</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;">56,480</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: -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;">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>

  </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="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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Roche (in thousands, 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;">2023</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; 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;">Revenue from our relationship with Roche</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;">48,838</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;">67,202</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;">17,241</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;">6</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</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>

  </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_SwedishOrphanBiovitrumABDistributionAgreementMember', window );">Sobi [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, 2023, 2022 and 2021, we earned the following revenue from our distribution agreement with Sobi for TEGSEDI in North America (in thousands, 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;">2023</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; 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;">TEGSEDI revenue from our distribution agreement with Sobi in North America</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;">2,646</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; 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;">4,004</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;">7,443</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: 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;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less than 1%</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;">1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989541049184">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 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_us-gaap_InvestmentsAbstract', window );"><strong>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_InvestmentsClassifiedByContractualMaturityDateTableTextBlock', window );">Contract Maturity of Available-for-Sale Securities</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 contract maturity of the available-for-sale securities we held as of December 31, 2023:</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;">68</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;">24</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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); 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: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);" 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%; background-color: rgb(255, 255, 255); border-bottom: 4px double rgb(0, 0, 0); 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, 2023</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;">559,967</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;">157</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;">(2,625</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;">557,499</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;">224,711</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;">64</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;">(611</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;">224,164</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;">513,784</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">152</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;">(1,889</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;">512,047</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;">17,757</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;">42</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;">(113</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;">17,686</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%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
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    <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">
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    <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;">415</div>
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    <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;">(5,238</div>
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    <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;">1,311,396</div>
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    <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">
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        </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;">243,151</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;">1,270</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;">(692</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;">243,729</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;">110,138</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;">547</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;">(21</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;">110,664</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;">294,873</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;">1,239</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;">(480</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;">295,632</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;">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: #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;">3,466</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</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;">(4</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;">3,469</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; margin-left: 18pt; 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: #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;">651,628</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;">3,063</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;">(1,197</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;">653,494</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: 27pt; 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: #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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,967,847</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,478</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,435</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,964,890</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;">Equity 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">&#160;</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">&#160;</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">&#160;</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">&#160;</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;">Publicly traded equity securities included in other current assets (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">
          <div style="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;">11,897</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;">236</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;">(5,832</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;">6,301</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;">Privately held securities included in deposits and other assets (3)</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;">23,115</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;">25,001</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;">(5,125</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;">42,991</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; margin-left: 18pt; 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: #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">
          <div style="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;" 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: #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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,237</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,957</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49,292</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; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; margin-left: 36pt; 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: #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">
          <div style="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: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,002,859</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">&#160;</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">
          <div style="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: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,715</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">&#160;</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">
          <div style="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: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(17,392</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>

    <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">
          <div style="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: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,014,182</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">&#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, 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>
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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: 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; margin-left: 18pt; 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>

    <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>
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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;">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; margin-left: 18pt; 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; margin-left: 36pt; 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; 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;">Publicly traded 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;">Privately held 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; margin-left: 18pt; 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; margin-left: 36pt; 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 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 publicly traded equity securities are included in other current
            assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2023, we recorded a $4.2 million net <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">unrealized loss in our consolidated statements of
              operations related to changes in the fair value of our investments in publicly traded companies.</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;">(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 privately held equity securities are included in deposits and other assets. We recognize our privately held 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, which are Level 3 inputs. In the year ended December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recorded a $</span>2.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million net unrealized gain in our consolidated statements of operations related to changes in the fair value of our investments in privately held companies.</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_DebtSecuritiesAvailableForSaleUnrealizedLossPositionFairValueTableTextBlock', 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, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;(in thousands, except for number of investments):</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; white-space: nowrap;" 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; white-space: nowrap;" 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;">297</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;">323,708</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;">(553</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;">178,183</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;">(2,764</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;">501,891</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;">(3,317</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;">63</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;">199,372</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;">(246</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;">14,777</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%; 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">
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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%; 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;">214,149</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;">(632</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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  </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;">34</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; 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;">325,966</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;">(1,031</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;">131,000</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;">(1,338</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;">456,966</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;">(2,369</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%; 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;">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; 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;">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>

    <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;">8,352</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; 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;">(17</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; 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;">7,888</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; 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;">(100</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; 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;">16,240</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; 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;">(117</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: 16%; padding-bottom: 4px; 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;">Total temporarily impaired securities</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%; border-bottom: #000000 double 4px; 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 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">455</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; 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;">857,398</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; 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;">(1,847</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; 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;">331,848</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; 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;">(4,588</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; 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;">1,189,246</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; 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;">(6,435</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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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of fair value 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. 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/exampleRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479081/326-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-6<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479106/326-30-50-4<br></p></div>
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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 maturities of an entity's investments as well as any other information pertinent to the investments.</p></div>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989542815840">
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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, 2023</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, 2023 and 2022&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. 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
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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, 2023</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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" 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>
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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; 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;">Observable Inputs</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; width: 64%; 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">185,424</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;">185,424</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>

  </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 (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;">801,228</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;">801,228</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 (3)</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;">334,828</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;">334,828</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 (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;">807,679</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;">807,679</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 (3)</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;">21,155</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;">21,155</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>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (5)</div>
          </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;">6,301</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;">6,301</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: 4px; background-color: #CCEEFF;" 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; 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;">2,156,615</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;">999,404</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;">1,157,211</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/>
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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; 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; white-space: nowrap;" 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, 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; white-space: nowrap;" 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; white-space: nowrap;" 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>

  </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;">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 (4)</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 (3)</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 (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;">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 (3)</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 (3)</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 (5)</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 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;">$33.0 million was included in cash and cash equivalents, 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;">(3)</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 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;">$11.0 million was included in cash and cash equivalents, 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;">(5)</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>
<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_FairValueAssetsMeasuredOnRecurringBasisTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 assets, including [financial] instruments measured at fair value that are classified in stockholders' equity, if any, by class that are measured at fair value on a recurring basis. The disclosures contemplated herein include the fair value measurements at the reporting date by the level within the fair value hierarchy in which the fair value measurements in their entirety fall, segregating fair value measurements using quoted prices in active markets for identical assets (Level 1), significant other observable inputs (Level 2), and significant unobservable inputs (Level 3).</p></div>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989540974976">
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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>
</tr>
<tr><th class="th"><div>Dec. 31, 2023</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_DebtDisclosureAbstract', window );"><strong>Long-Term Obligations and Commitments [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_ScheduleOfDebtInstrumentsTextBlock', window );">Long-Term Obligations</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 carrying value of our long-term obligations was as follows (in thousands):</div>

<div><br/>
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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"> </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>

  </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;">2023</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;">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>

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  <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;">1.75</span>%
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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;">562,285</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>

  </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</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;">625,380</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;">622,242</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;"><span style="text-indent: 0pt;">0.125</span>%
            convertible senior notes</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;">&#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;">544,504</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;">Liability related to sale of future royalties</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;">513,736</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;">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;">178,969</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;">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>

  </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;">8,859</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;">8,998</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;">33,714</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;">7,295</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>

  </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;">1,922,943</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;">1,369,195</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;">(8,831</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;">(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>

  </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;">1,914,112</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;">1,361,660</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </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_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, 2023 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;">2024</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;">55,298</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;">2025</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;">10,657</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;">2026</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;">643,157</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;">2027</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;">10,509</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;">2028</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;">580,277</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;">8,462</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;">1,308,360</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: 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;">(157</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;">(47,138</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;">(20,061</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 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;">1,241,004</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; white-space: nowrap;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At December 31, 2023</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;">171.9</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: 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;">179.0</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;">13.0 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, 2023,
    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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" 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;">2024</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;">20,398</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;">2025</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;">20,645</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;">2026</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;">20,781</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;">2027</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;">20,800</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;">2028</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;">20,774</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;">176,138</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;">279,536</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;">(100,567</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;">(8,094</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;">170,875</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_OtherNoncurrentLiabilitiesTableTextBlock', window );">Liability Related to Sale of Future Royalties</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 liability related to
      sale of future royalties for the year ended </span>December 31, 2023<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: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of future royalties</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;">500,000</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;">Royalty payments to Royalty Pharma</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;">(44,628</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: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense related to sale of future royalties</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;">68,238</div>
        </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>

  </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;">Liability related to sale of future royalties as of December 31, 2023</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;">523,610</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance costs related to sale of future royalties</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;">(10,434</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: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of issuance costs related to sale of future royalties as of December 31, 2023</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;">560</div>
        </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>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net liability related to sale of future royalties as of December 31, 2023</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;">513,736</div>
        </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">&#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_ConvertibleSeniorNotes175PercentMember', window );">1.75% Notes [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_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_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, 2023, we had the following 1.75%
    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"> </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" 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;">1.75% 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;">575.0</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: 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;">12.7</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_6bfb094eab7041389566a848570cbbe5">June 2028</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; width: 88%;" 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; 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;">1.75</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: top; width: 88%; 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; 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;">2.3</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: 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;">53.73</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;">Total shares of common stock subject to conversion</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;">10.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </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, 2023, 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"> </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;">7.2</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: 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_77100aa329424b42b6f03dc4fa1e2472">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; width: 88%;" 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; 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;">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: top; width: 88%; 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; 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;">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: 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>
<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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [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_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_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, 2023, 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"> </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;">44.5</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;">0.2</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: 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_5c75d58f5a434990850c3cf960d7b0c3">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; width: 88%;" 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; 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;">0.125</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: top; width: 88%; 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; 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;">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: 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, excluding shares related to <span style="text-indent: 0pt;">0.125</span>% Notes we have repurchased and are currently holding in treasury</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;">0.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


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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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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>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.</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 );">- Definition</a><div><p>Tabular disclosure of contractual obligation by timing of payment due. Includes, but is not limited to, long-term debt obligation, lease obligation, and purchase 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/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (S-X 210.12-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-3<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of convertible debt instrument. Includes, but is not limited to, principal amount and amortized premium or discount.</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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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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  <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;">(1,842</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;">55.90</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, 2023</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;">14,091</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;">48.43</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;">4.74</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;">78,542</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, 2023</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;">9,703</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;">52.24</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;">3.20</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;">28,349</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_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, 2023 (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; white-space: nowrap;" 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, 2022</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;">2,766</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;">48.30</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;">1,707</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;">40.51</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;">(1,055</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;">51.64</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;">(179</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;">42.90</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, 2023</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;">3,239</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;">43.40</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, 2023 (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; white-space: nowrap;" 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, 2022</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;">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">
          <div style="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;">52.59</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: 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;">158</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;">57.43</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</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;">(75</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%; padding-bottom: 2px; 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: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.43</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; 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, 2023</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;">226</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;">56.04</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_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, 2023, 2022 and 2021 (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;">2023</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; 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;">499</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;">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>

  </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;">77,826</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;">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>

  </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;">27,484</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;">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>

  </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;">105,809</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;">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>

  </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;">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;">2023</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; 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;">3.8</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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>

  </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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46.8</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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>

  </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;">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>

  </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;">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;">2023</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; 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;">3.8</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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>

  </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;">52.7</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;">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>

  </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;">7.7 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;">7.4 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>

  </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_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;">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;">2023</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; 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;">5.3</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;">0.1</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>

  </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>

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  <tr>

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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%; 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;">742</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;">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>

  </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;">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;">(333,965</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;">(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>

  </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_ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock', window );">Income Tax Expense (Benefit)</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 income tax expense (benefit) 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="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;">2023</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;" 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;">35,861</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;">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>

  </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;">(3,687</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;">1,129</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>

  </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;">147</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;">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>

  </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;">32,321</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;">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>

  </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;">&#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%; 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;">&#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: -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;">32,321</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;">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>

  </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="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; 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 loss before income 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;">2023</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;">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>

  </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;">Pre-tax loss</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;">(333,965</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;">(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>

  </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;">(70,133</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;">(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>

  </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;">(22,597</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;">6.8</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;">(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>
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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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    <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">
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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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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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>

  </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">
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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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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">
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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>
        </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;">Loss on debt transactions</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>

    <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">
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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">
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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">
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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;">(0.9</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; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax credits</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;">(67,131</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">
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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;">(39,729</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;">15.4</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">(23,198</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;">79.6</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">
          <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;">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">&#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>
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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;">(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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24</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;">0.1</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">
          <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;">1,023</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;">(0.3</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; text-align: right; width: 9%;" valign="bottom">
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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="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>

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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">
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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">
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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>

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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">
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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">
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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">
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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">
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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">&#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>

  </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;">Foreign-derived intangible income benefit</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;">(7,493</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;">2.2</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">
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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">
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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">&#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: 28%;" valign="bottom">
          <div style="text-align: left; 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;">19,546</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;">(5.9</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">14,030</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;">(5.4</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;">4,720</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;">(16.2</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%; 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(405</div>
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    <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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">364</div>
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    <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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,503</div>
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    <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>
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    <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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); 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: 4px double rgb(0, 0, 0);" valign="bottom">
          <div style="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: 4px double rgb(0, 0, 0);" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,321</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: 4px double rgb(0, 0, 0);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); white-space: 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: 4px double rgb(0, 0, 0);" valign="bottom">
          <div style="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: 4px double rgb(0, 0, 0);" 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: 4px double rgb(0, 0, 0);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" 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%; border-bottom: 4px double rgb(0, 0, 0); white-space: 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: 4px double rgb(0, 0, 0);" valign="bottom">
          <div style="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: 4px double rgb(0, 0, 0);" 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: 4px double rgb(0, 0, 0);" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" 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%; border-bottom: 4px double rgb(0, 0, 0); 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, 2023 and 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; 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;">2023</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>

  </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>

  </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 operating loss carryovers</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;">77,964</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;">87,802</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;">Tax credits</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;">239,962</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;">277,436</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;">71,683</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;">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>

  </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;">77,468</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;">86,983</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;">104,380</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;">104,649</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </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;">16,849</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;">34,384</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;">Capitalized research and development 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;">238,738</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;">119,635</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;">Long-term 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">&#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;">43,718</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;">45,612</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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sale of future royalties</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;">144,608</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: 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;">10,343</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;">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>

  </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;">1,025,713</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;">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>

  </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;">(4,166</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;">(4,475</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>

  </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;">(42,007</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;">(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>

  </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;">(1,910</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;">(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>

  </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;">977,630</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;">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>

  </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;">(977,630</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;">(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>

  </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;">2023</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; 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;">56,567</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;">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>

  </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 lapse of statute of limitations</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;">(14,993</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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: 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%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">(737</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;">(267</div>
        </td>

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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%; 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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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,032</div>
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    <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;">1,490</div>
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    <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;">1,354</div>
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    <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">
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    <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">
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<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>
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<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>
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<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
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        </td>

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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">
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        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">330,627</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">
          <div style="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>

  </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">
          <div style="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;">(6,122</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;">(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>

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  <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 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">
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        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,263</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;">(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>

  </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 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;">(0.06</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;">(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>

  </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 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;">(0.06</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;">(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>

  </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 higher in the three months ended December 31, 2023
            compared to the same period in 2022 primarily due to the $50 million milestone payment we earned from AstraZeneca when the FDA approved
            WAINUA for ATTRv-PN in the U.S., $36 million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth
            quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis.</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 lower in the three months ended December 31,
            2023 compared to the same period in 2022 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>

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  <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 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 loss per share by dividing the total net 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 incurred a net loss for the fourth quarter of 2023 and 2022. As a
            result, 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.</div>
        </td>

  </tr>


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<th class="th" colspan="2">12 Months Ended</th>
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<th class="th"><div>Dec. 31, 2023</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="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>
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<td class="nump">82.50%<span></span>
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<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_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>
</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_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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_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>
</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_ContractWithCustomerAssetNetCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
</table>
<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>
</body>
</html>
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</DOCUMENT>
<DOCUMENT>
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<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989543264576">
<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, 2023</div></th>
<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_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">$ 78.2<span></span>
</td>
<td class="nump">$ 73.5<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_ContractWithCustomerLiabilityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ContractWithCustomerLiabilityAbstract</td>
</tr>
<tr>
<td style="padding-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_ContractWithCustomerLiabilityRevenueRecognized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td style="padding-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>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>64
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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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989541057216">
<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, 2023</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_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">$ 4.3<span></span>
</td>
<td class="nump">$ 4.7<span></span>
</td>
<td class="nump">$ 5.3<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PatentExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<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>
</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>
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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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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ResearchAndDevelopmentExpenseAbstract">
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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 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>
</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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</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
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<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538517056">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details)<br></strong></div></th>
<th class="th"><div>Dec. 31, 2023</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, 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% 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_EarningsPerShareBasicAbstract', window );"><strong>Basic and Diluted Net Loss 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>
<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_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
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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>
</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_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>
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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_EarningsPerShareBasicAbstract', window );"><strong>Basic and Diluted Net Loss 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>
<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">0.125%<span></span>
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<td class="nump">0.125%<span></span>
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<td class="nump">0.125%<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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75% 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_EarningsPerShareBasicAbstract', window );"><strong>Basic and Diluted Net Loss 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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">1.75%<span></span>
</td>
<td class="nump">1.75%<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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<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> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br></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">
<tr>
<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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<head>
<title></title>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989534792992">
<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, 2023 </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>
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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 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]</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_TermOfAlternativePayoutMechanism', window );">Term of Alternative Calculation</a></td>
<td class="text">3 years<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_MeasurementPeriodForAlternativePayoutMechanism', window );">Measurement period for Alternative Calculation</a></td>
<td class="text">3 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]</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>
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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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">3 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] | One-Year Period [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">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_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="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">3 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] | Granted 2020 through 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 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)</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] | Granted 2020 through 2022 [Member] | Minimum [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">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] | Granted 2020 through 2022 [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_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">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] | Granted 2020 through 2022 [Member] | One-Year Period [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_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">33.30%<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] | Granted 2020 through 2022 [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="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] | Granted 2020 through 2022 [Member] | Three-Year Period [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_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">33.30%<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] | Granted in 2023 [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">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_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest', window );">Number of units guaranteed to vest (in 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] | Granted in 2023 [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] | Granted in 2023 [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">200.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MeasurementPeriodForAlternativePayoutMechanism">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Measurement period for alternative payout mechanism, or the Alternative Calculation, included in equity-based award, 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_MeasurementPeriodForAlternativePayoutMechanism</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_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_ions_TermOfAlternativePayoutMechanism">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 an alternative three-year payout mechanism, or the Alternative Calculation, included in equity-based award, 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_TermOfAlternativePayoutMechanism</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_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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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">
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_Granted2020Through2022Member</td>
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<td><strong> Name:</strong></td>
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<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_GrantedIn2023Member</td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538617856">
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<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, 2023 </div>
<div>Company</div>
</th>
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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_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of publicly held companies in which there is an equity ownership interest of less than 20%</a></td>
<td class="nump">3<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_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of privately held companies in which there is an equity ownership interest of less than 20%</a></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 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>
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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 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>
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<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>
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<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_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_CashCashEquivalentsAndShortTermInvestmentsAbstract</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>
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<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>68
<FILENAME>R39.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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989534455008">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Property, Plant and Equipment (Details)<br></strong></div></th>
<th class="th"><div>Dec. 31, 2023</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_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember', window );">Computer Software, Laboratory, Manufacturing and Other Equipment [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_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [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_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">3 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_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember', window );">Computer Software, Laboratory, Manufacturing and Other Equipment [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_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [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_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</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_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember', window );">Building, Building Improvements and Building Systems [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_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [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_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">15 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_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember', window );">Building, Building Improvements and Building Systems [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_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [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_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">40 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_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandImprovementsMember', window );">Land Improvements [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_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [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_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">20 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_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember', window );">Leasehold Improvements [Member] | Minimum [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_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [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_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">5 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_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember', window );">Leasehold Improvements [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_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [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_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">15 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_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember', window );">Furniture and Fixtures [Member] | Minimum [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_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [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_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">5 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_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember', window );">Furniture and Fixtures [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_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [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_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">10 years<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_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_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>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_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>
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<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>
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<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>
</div>
</body>
</html>
</TEXT>
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<DOCUMENT>
<TYPE>XML
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538532800">
<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, 2023</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, 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">3<span></span>
</td>
<td class="text">&#160;<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="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_ConvertibleSeniorNotes175PercentMember', window );">1.75% 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>
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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_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>
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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_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<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="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>
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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_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>
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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">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>
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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_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>
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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_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>
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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_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="nump">0.125%<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">0.125%<span></span>
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<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>
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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> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br></p></div>
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<FILENAME>R41.htm
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989537765552">
<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, 2023</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, 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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [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>
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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_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>
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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_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>
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<td class="nump">0.00%<span></span>
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<td class="nump">0.00%<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>
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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_GeneralDiscussionOfDerivativeInstrumentsAndHedgingActivitiesAbstract', window );"><strong>Call Spread [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>
</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_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
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<td class="nump">0.125%<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 );">- 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> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br></p></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_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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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td></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 );">- 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>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Segment Information (Details)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th">
<div>Dec. 31, 2023 </div>
<div>Segment</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>
</tr>
<tr class="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>
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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 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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-18<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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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<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_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract</td>
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<td>xbrli:stringItemType</td>
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<td>na</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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989539151040">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Supplemental Financial Data, Inventories (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<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_InventoryNetAbstract', window );"><strong>Inventory [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_InventoryRawMaterials', window );">Raw materials</a></td>
<td class="nump">$ 22,794<span></span>
</td>
<td class="nump">$ 19,760<span></span>
</td>
</tr>
<tr class="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">5,477<span></span>
</td>
<td class="nump">2,109<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryFinishedGoods', window );">Finished goods</a></td>
<td class="nump">154<span></span>
</td>
<td class="nump">164<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_InventoryNet', window );">Total inventory</a></td>
<td class="nump">28,425<span></span>
</td>
<td class="nump">22,033<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_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>
</tr>
<tr class="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">20,985<span></span>
</td>
<td class="nump">17,061<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_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>
</td>
</tr>
<tr class="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">$ 1,809<span></span>
</td>
<td class="nump">$ 2,699<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_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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_InventoryFinishedGoods</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<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 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/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481372/852-10-55-10<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483467/210-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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>
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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 class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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>
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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>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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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>
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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_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember</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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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;">us-gaap_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember</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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989537794800">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Supplemental Financial Data, Property, Plant and Equipment (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<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_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>
</tr>
<tr class="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="num">$ (96,759)<span></span>
</td>
<td class="num">$ (87,716)<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="nump">71,043<span></span>
</td>
<td class="nump">74,294<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>
</tr>
<tr class="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>
</tr>
<tr class="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="nump">159,233<span></span>
</td>
<td class="nump">153,441<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="nump">62,474<span></span>
</td>
<td class="nump">65,725<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>
</tr>
<tr class="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>
</tr>
<tr class="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="nump">79,885<span></span>
</td>
<td class="nump">74,351<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>
</tr>
<tr class="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>
</tr>
<tr class="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="nump">41,228<span></span>
</td>
<td class="nump">41,158<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>
</tr>
<tr class="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>
</tr>
<tr class="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="nump">28,276<span></span>
</td>
<td class="nump">28,357<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>
</tr>
<tr class="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>
</tr>
<tr class="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="nump">9,844<span></span>
</td>
<td class="nump">9,575<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>
</tr>
<tr class="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>
</tr>
<tr class="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="nump">$ 8,569<span></span>
</td>
<td class="nump">$ 8,569<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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(14))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482099/360-10-50-1<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;">us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment</td>
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<td>xbrli:monetaryItemType</td>
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<td>credit</td>
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<td>instant</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_PropertyPlantAndEquipmentAbstract</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 );">- 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> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(13))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 360<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482099/360-10-50-1<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;">us-gaap_PropertyPlantAndEquipmentGross</td>
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<td>instant</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 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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 360<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482099/360-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 852<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481372/852-10-55-10<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 360<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480842/942-360-50-1<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;">us-gaap_PropertyPlantAndEquipmentNet</td>
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<td>xbrli:monetaryItemType</td>
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<td>debit</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>
<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>
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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>
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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_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember</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>
<td>na</td>
</tr>
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<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>
</table>
</div>
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</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>74
<FILENAME>R45.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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</head>
<body>
<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538628080">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Supplemental Financial Data, Accrued Liabilities (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<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_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_AccruedClinicalDevelopmentExpenses', window );">Clinical expenses</a></td>
<td class="nump">$ 105,967<span></span>
</td>
<td class="nump">$ 116,460<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">7,454<span></span>
</td>
<td class="nump">7,945<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">4,875<span></span>
</td>
<td class="nump">3,498<span></span>
</td>
</tr>
<tr class="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">29,598<span></span>
</td>
<td class="nump">12,198<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">$ 147,894<span></span>
</td>
<td class="nump">$ 140,101<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedClinicalDevelopmentExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 development 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_AccruedClinicalDevelopmentExpenses</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> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>75
<FILENAME>R46.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">
							function toggleNextSibling (e) {
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</head>
<body>
<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538372224">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Revenues (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2023 </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 ($) </div>
<div>Component </div>
<div>PerformanceObligation</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<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_AstraZenecaCollaborationWainuaMember', window );">WAINUA (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>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 20,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<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_NumberOfMaterialComponents', window );">Number of material components | Component</a></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_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="nump">1<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="nump">$ 200,000<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_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>
</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_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_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 308,591<span></span>
</td>
<td class="nump">303,358<span></span>
</td>
<td class="nump">342,395<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_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">240,379<span></span>
</td>
<td class="nump">242,314<span></span>
</td>
<td class="nump">267,776<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_OtherCommercialMember', window );">Other 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_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">68,212<span></span>
</td>
<td class="nump">61,044<span></span>
</td>
<td class="nump">74,619<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="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">34,913<span></span>
</td>
<td class="nump">30,051<span></span>
</td>
<td class="nump">55,500<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_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="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">33,299<span></span>
</td>
<td class="nump">30,993<span></span>
</td>
<td class="nump">19,119<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_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="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">479,056<span></span>
</td>
<td class="nump">284,009<span></span>
</td>
<td class="nump">468,061<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="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">352,657<span></span>
</td>
<td class="nump">207,222<span></span>
</td>
<td class="nump">468,061<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_WainuaJointDevelopmentRevenueMember', window );">WAINUA 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="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 126,399<span></span>
</td>
<td class="nump">$ 76,787<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_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_us-gaap_DisaggregationOfRevenueAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_DisaggregationOfRevenueAbstract</td>
</tr>
<tr>
<td style="padding-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_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> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479941/924-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-5<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-40<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-41<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_AstraZenecaCollaborationWainuaMember</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_CommercialMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_CommercialMember</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_SpinrazaRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_SpinrazaRoyaltiesMember</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_OtherCommercialMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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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<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>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember</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_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember">
<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">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember</td>
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<td><strong> Balance 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">
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<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_CollaborativeAgreementRevenueMember</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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<DOCUMENT>
<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989527298608">
<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">3 Months Ended</th>
<th class="th" colspan="7">12 Months Ended</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>Dec. 31, 2023 </div>
<div>USD ($) </div>
<div>Medicine</div>
</th>
<th class="th">
<div>Jun. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($) </div>
<div>Medicine</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</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, 2017 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2013 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2012 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Program</div>
</th>
<th class="th">
<div>Jan. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Apr. 30, 2018 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Sep. 30, 2013 </div>
<div>USD ($) </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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_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>
</tr>
<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>
</tr>
<tr class="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">240,379<span></span>
</td>
<td class="nump">242,314<span></span>
</td>
<td class="nump">267,776<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
</tr>
<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>
</tr>
<tr class="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">479,056<span></span>
</td>
<td class="nump">284,009<span></span>
</td>
<td class="nump">468,061<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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>
</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="nump">$ 1,500,000<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>
<td class="text">&#160;<span></span>
</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="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]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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>
</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="nump">25.00%<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="nump">25.00%<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_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="nump">$ 475,000<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
<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]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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>
</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="nump">45.00%<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
<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="nump">$ 550,000<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
<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>
</tr>
<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>
</tr>
<tr class="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">350,146<span></span>
</td>
<td class="nump">366,696<span></span>
</td>
<td class="nump">$ 428,784<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">307,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 307,400<span></span>
</td>
<td class="nump">$ 351,200<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>
<td class="text">&#160;<span></span>
</td>
<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>
</tr>
<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>
</tr>
<tr class="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">44.00%<span></span>
</td>
<td class="nump">62.00%<span></span>
</td>
<td class="nump">53.00%<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="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] | 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>
</tr>
<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>
</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="nump">3,800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 3,800,000<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>
<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>
</tr>
<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>
</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="nump">2,100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,100,000<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>
</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="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>
<td class="text">&#160;<span></span>
</td>
<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>
</tr>
<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>
</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="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>
<td class="text">&#160;<span></span>
</td>
<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>
</tr>
<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>
</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="nump">1,600,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,600,000<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>
<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>
</tr>
<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>
</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="nump">425,000<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="text">&#160;<span></span>
</td>
<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>
</tr>
<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>
</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="nump">85,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="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_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="nump">45,000<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="text">&#160;<span></span>
</td>
<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>
</tr>
<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>
</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="nump">555,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">45,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">110,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">400,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
</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>
</tr>
<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>
</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="nump">1,100,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">$ 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>
<td class="text">&#160;<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="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
<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_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">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>
<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_UpfrontPaymentReceivedIncludingPurchaseOfStock', window );">Upfront payment received, including purchase of stock</a></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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="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>
<td class="text">&#160;<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_PercentageCashPremiumPaidOnSharesPurchased', window );">Percentage cash premium paid on shares purchased</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>
<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_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration', window );">Maximum amount of payments receivable per medicine over term of collaboration</a></td>
<td class="nump">270,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration', window );">Maximum amount of license fees per medicine over term of collaboration</a></td>
<td class="nump">15,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration', window );">Maximum amount of development milestone payments per medicine over term of collaboration</a></td>
<td class="nump">105,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments per medicine over term of collaboration</a></td>
<td class="nump">150,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">15,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="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>
<td class="text">&#160;<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="nump">623,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">623,000<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="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="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
</tr>
<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>
</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="nump">325,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">325,000<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="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="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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="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="text">&#160;<span></span>
</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">$ 100,000<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_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="nump">$ 70,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="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>
<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="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration', window );">Maximum amount of payments receivable per antisense molecule over term of collaboration</a></td>
<td class="nump">$ 260,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration', window );">Maximum amount of license fees per antisense molecule over term of collaboration</a></td>
<td class="nump">70,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration', window );">Maximum amount of development milestone payments per antisense molecule over term of collaboration</a></td>
<td class="nump">60,000<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="re">
<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="nump">$ 130,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
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</td>
<td class="nump">$ 16,000<span></span>
</td>
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</td>
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</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="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_NumberOfMedicinesCurrentlyBeingAdvanced', window );">Number of medicines currently being advanced | Medicine</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="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>
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</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="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>
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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_NumberOfMedicinesCurrentlyBeingAdvanced', window );">Number of medicines currently being advanced | Medicine</a></td>
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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>
</td>
<td class="text">&#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_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>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">$ 110,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">35,000<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">18,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">18,000<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="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="nump">55,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">55,000<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>
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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_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="nump">20,000<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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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>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#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>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#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="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="nump">11.00%<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>
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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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</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_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology [Member] | QALSODY [Member] | 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>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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>
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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>
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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_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="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>
<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>
</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_BiogenCollaboration2012NeurologyMember', window );">2012 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>
</tr>
<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>
</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="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="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="nump">210,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">70,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">10,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">130,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="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>
</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="nump">70,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized', window );">Number of programs under which medicines are to be developed and commercialized | 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>
</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>
</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] | 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>
</tr>
<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>
</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="nump">230,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">230,000<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_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>
</tr>
<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>
</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="nump">57,000<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 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="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>
</tr>
<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>
</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="nump">$ 68,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">68,000<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="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="nump">$ 39,000<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>
</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_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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-2<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;">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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479941/924-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-5<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-40<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-41<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_SpinrazaRoyaltiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_SpinrazaRoyaltiesMember</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_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_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>
</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_TypeOfArrangementAxis=ions_BiogenCollaborationsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_BiogenCollaborationsMember</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_BiogenCollaborationSpinrazaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_BiogenCollaborationSpinrazaMember</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_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember</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_Ion306Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_Ion306Member</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_BiogenCollaboration2018StrategicNeurologyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_BiogenCollaboration2018StrategicNeurologyMember</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_BiogenCollaboration2013StrategicNeurologyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_BiogenCollaboration2013StrategicNeurologyMember</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_MedicinesForParkinsonsDiseaseMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989537242016">
<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="4">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2023 </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 ($) </div>
<div>Component </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2015 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jul. 31, 2015 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<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_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>
</tr>
<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">202,236<span></span>
</td>
<td class="nump">79,160<span></span>
</td>
<td class="nump">$ 254,591<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">$ 0<span></span>
</td>
<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_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>
</tr>
<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="nump">26.00%<span></span>
</td>
<td class="nump">13.00%<span></span>
</td>
<td class="nump">31.00%<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_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember', window );">WAINUA (Eplontersen) [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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="nump">$ 3,600,000<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>
</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="nump">$ 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 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="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>
</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="nump">485,000<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 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="nump">$ 2,900,000<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>
</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="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>
</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="text">&#160;<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="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="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 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="nump">$ 200,000<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_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>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="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>
</tr>
<tr class="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">20,000<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="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_AstraZenecaCollaborationWainuaMember', window );">WAINUA (Eplontersen) [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_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_CumulativePaymentsReceived', window );">Cumulative payments received</a></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>
<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_AstraZenecaCollaborationWainuaMember', window );">WAINUA (Eplontersen) [Member] | ATTRv-PN [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">50,000<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_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember', window );">Cardiovascular, Renal and Metabolic 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>
</tr>
<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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></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>
</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="nump">$ 65,000<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="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>
<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="nump">865,000<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 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="nump">2,200,000<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>
</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="nump">1<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="nump">$ 65,000<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_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></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>
</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="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>
</tr>
<tr class="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">36,000<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_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember', window );">Cardiovascular, Renal and Metabolic Diseases [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_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_CumulativePaymentsReceived', window );">Cumulative payments received</a></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>
</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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-2<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;">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> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479941/924-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-5<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-40<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-41<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_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_AstraZenecaCollaborationWainuaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_AstraZenecaCollaborationWainuaMember</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">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
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<td><strong> Balance 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;">srt_ProductOrServiceAxis=ions_AttrvPnMember</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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<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>
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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>
<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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<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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989540958624">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, GSK (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="4">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2023</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, 2010</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>
</tr>
<tr class="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">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<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]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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>
</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="nump">$ 35,000<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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></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>
</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="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="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="nump">42,500<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="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="nump">120,000<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="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>
</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="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>
</tr>
<tr class="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">15,000<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_ContractWithCustomerLiability', window );">Deferred revenue</a></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_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>
</tr>
<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>
</tr>
<tr class="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="nump">2.00%<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="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] | 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>
</tr>
<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>
</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="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>
</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>
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<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>
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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 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>
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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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<tr>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</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_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>
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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>debit</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_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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<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_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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-2<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;">us-gaap_ContractWithCustomerLiability</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>
<td>instant</td>
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<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> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479941/924-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-5<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-40<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-41<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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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<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_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>
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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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<tr>
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<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</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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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</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>
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<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">3 Months Ended</th>
<th class="th" colspan="4">12 Months Ended</th>
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<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
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<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($)</div>
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<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
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<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
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<div>Dec. 31, 2017 </div>
<div>USD ($) </div>
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<div>Aug. 31, 2023 </div>
<div>PerformanceObligation</div>
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<div>Mar. 31, 2017 </div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 587,367<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_ProductOrServiceAxis=ions_PelacarsenActivePharmaceuticalIngredientMember', window );">Pelacarsen API [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="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>
</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="nump">25.00%<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>
</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_NovartisCollaborationPelacarsenMember', window );">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>
<td class="text">&#160;<span></span>
</td>
</tr>
<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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="nump">$ 900,000<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>
</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="nump">$ 75,000<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="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>
</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="nump">25,000<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_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="nump">290,000<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>
<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="nump">360,000<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>
<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="nump">275,000<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>
<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="nump">50,000<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</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_ProceedsFromSaleOfCommonStockIncludingPremiumPaid', window );">Proceeds from sale 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="nump">$ 100,000<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_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">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_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="nump">108,400<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_PremiumReceivedOnSharesIssued', window );">Premium received on shares issued</a></td>
<td class="text">&#160;<span></span>
</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">28,400<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_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture', window );">Potential premium received if common stock was purchased in the future</a></td>
<td class="text">&#160;<span></span>
</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">5,000<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">30,194<span></span>
</td>
<td class="nump">237<span></span>
</td>
<td class="nump">$ 25,526<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" 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">30,000<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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_NovartisCollaborationPelacarsenMember', window );">Pelacarsen [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="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_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3.00%<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_NovartisCollaborationPelacarsenMember', window );">Pelacarsen [Member] | Maximum [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="text">&#160;<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>
<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_NovartisCollaborationPelacarsenMember', window );">Pelacarsen [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>
<td class="text">&#160;<span></span>
</td>
</tr>
<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_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="nump">64,000<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_NovartisCollaborationPelacarsenMember', window );">Pelacarsen [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>
<td class="text">&#160;<span></span>
</td>
</tr>
<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_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="nump">40,100<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_NovartisCollaborationPelacarsenMember', window );">Pelacarsen [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>
<td class="text">&#160;<span></span>
</td>
</tr>
<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_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 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="nump">1,500<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_NovartisCollaborationPelacarsenMember', window );">Pelacarsen [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>
<td class="text">&#160;<span></span>
</td>
</tr>
<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_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="nump">$ 2,800<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_NovartisCollaborationLpADrivenCardiovascularDiseaseMember', window );">Lp(a)-Driven Cardiovascular 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>
</tr>
<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="nump">730,000<span></span>
</td>
<td class="nump">$ 730,000<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">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>
</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="nump">155,000<span></span>
</td>
<td class="nump">155,000<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="nump">105,000<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_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="nump">410,000<span></span>
</td>
<td class="nump">410,000<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_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">60,000<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="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="nump">5,000<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>
<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="nump">1<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">$ 60,000<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="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_NovartisCollaborationLpADrivenCardiovascularDiseaseMember', window );">Lp(a)-Driven Cardiovascular Disease [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>
</tr>
<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_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</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>
</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_NovartisCollaborationLpADrivenCardiovascularDiseaseMember', window );">Lp(a)-Driven Cardiovascular Disease [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>
</tr>
<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_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>
</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_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_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 was 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_PotentialPremiumReceivedIfCommonStockWasPurchasedInFuture</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_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_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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-2<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;">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> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479941/924-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-5<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-40<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-41<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<tr>
<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_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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481112/505-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 505<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481004/946-505-50-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-3<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-03(i)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479886/946-10-S99-3<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480008/505-10-S99-1<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_StockIssuedDuringPeriodSharesNewIssues</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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_PelacarsenActivePharmaceuticalIngredientMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
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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_NovartisCollaborationPelacarsenMember</td>
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<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</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">
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<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForPelacarsenMember</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;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForOlezarsenMember</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;">srt_ProductOrServiceAxis=ions_OlezarsenActivePharmaceuticalIngredientMember</td>
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<tr>
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<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationLpADrivenCardiovascularDiseaseMember</td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989534883120">
<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">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">
<div>Dec. 31, 2023 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Program </div>
<div>Indication</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Program </div>
<div>Indication</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>Oct. 31, 2018 </div>
<div>PerformanceObligation</div>
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<th class="th">
<div>Dec. 31, 2013 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<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>
</tr>
<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="nump">48,838<span></span>
</td>
<td class="nump">67,202<span></span>
</td>
<td class="nump">$ 17,241<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 36,700<span></span>
</td>
<td class="nump">$ 36,700<span></span>
</td>
<td class="nump">$ 22,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</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>
</tr>
<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="nump">6.00%<span></span>
</td>
<td class="nump">11.00%<span></span>
</td>
<td class="nump">2.00%<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_TypeOfArrangementAxis=ions_RocheCollaborationHuntingtonsDiseaseMember', window );">HD [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_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="nump">395,000<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>
</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="nump">30,000<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>
</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="nump">45,000<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>
</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="nump">70,000<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>
</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="nump">170,000<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>
</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="nump">80,000<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>
</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_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration', window );">Maximum amount of milestone payments for each additional medicine successfully developed over term of collaboration</a></td>
<td class="nump">136,500<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>
</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="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>
</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="nump">17,500<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>
</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>
</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">$ 30,000<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_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>
</tr>
<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="nump">810,000<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>
</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="nump">75,000<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="nump">35,000<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>
</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="nump">145,000<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>
</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="nump">279,000<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>
</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="nump">280,000<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>
</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="nump">135,000<span></span>
</td>
<td class="nump">135,000<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 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="nump">90,000<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>
</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="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_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="nump">$ 97,000<span></span>
</td>
<td class="nump">$ 97,000<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_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">$ 22,000<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_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="nump">2<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_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>
</tr>
<tr class="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">$ 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>
</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>
</tr>
<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_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="nump">1<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="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>
</tr>
<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_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="nump">1<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="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_RocheCollaborationRNATargetedProgramsForADAndHDMember', window );">RNA-targeted Programs for AD and HD [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="nump">$ 625,000<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>
</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">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="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="nump">167,000<span></span>
</td>
<td class="nump">167,000<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 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="nump">398,000<span></span>
</td>
<td class="nump">398,000<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_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="nump">60,000<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>
</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="nump">$ 7,500<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>
</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_NumberOfEarlyStagePrograms', window );">Number of early-stage programs | Program</a></td>
<td class="nump">2<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="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">2<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_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 60,000<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>
</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_RocheCollaborationRNATargetedProgramsForADAndHDMember', window );">RNA-targeted Programs for AD and HD [Member] | R&amp;D Services for Investigational Medicine for AD [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="nump">45,000<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>
</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_RocheCollaborationRNATargetedProgramsForADAndHDMember', window );">RNA-targeted Programs for AD and HD [Member] | R&amp;D Services for Investigational Medicine for HD [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="nump">$ 15,000<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>
</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_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_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_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_NumberOfEarlyStagePrograms">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 early-stage programs to be developed for RNA-targeting investigational medicines for the treatment of Alzheimer's disease (AD) and Huntington's disease (HD).</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_NumberOfEarlyStagePrograms</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_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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-2<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;">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> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479941/924-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-5<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-40<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-41<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_TypeOfArrangementAxis=ions_RocheCollaborationsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_RocheCollaborationsMember</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_RocheCollaborationHuntingtonsDiseaseMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_RocheCollaborationHuntingtonsDiseaseMember</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_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember</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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<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 border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_GeographicAtrophyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_GeographicAtrophyMember</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_ImmunoglobulinANephropathyMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ImmunoglobulinANephropathyMember</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_TypeOfArrangementAxis=ions_RocheCollaborationRNATargetedProgramsForADAndHDMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_RocheCollaborationRNATargetedProgramsForADAndHDMember</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_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ResearchAndDevelopmentServicesForInvestigationalMedicineForAlzheimerSDiseaseMember</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_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ResearchAndDevelopmentServicesForInvestigationalMedicineForHuntingtonSDiseaseMember</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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<title></title>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989527039440">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Otsuka (Details)<br> $ in Thousands</strong></div></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, 2023 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($) </div>
<div>PerformanceObligation</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>
</tr>
<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>
</tr>
<tr class="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">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<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_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [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_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>
</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="nump">$ 185,000<span></span>
</td>
<td class="nump">185,000<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">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>
</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="nump">50,000<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="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="nump">70,000<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="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="nump">65,000<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>
</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="nump">$ 15,000<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="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">2<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 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">$ 65,000<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>
</tr>
<tr class="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">56,480<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">8,500<span></span>
</td>
<td class="nump">$ 8,500<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_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [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>
</tr>
<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>
</tr>
<tr class="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">7.00%<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_TypeOfArrangementAxis=ions_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [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>
</tr>
<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>
</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>
</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_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [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>
</tr>
<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>
</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="nump">30.00%<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_TypeOfArrangementAxis=ions_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [Member] | License of Donidalorsen [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="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>
</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">56,000<span></span>
</td>
<td class="nump">$ 56,000<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_OtsukaPharmaceuticalCoLtdCollaborationMember', window );">Otsuka [Member] | R&amp;D Services for Donidalorsen [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_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>
</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">$ 9,000<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>
</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_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_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_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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-2<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;">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> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479941/924-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-5<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-40<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-41<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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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<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_TypeOfArrangementAxis=ions_OtsukaPharmaceuticalCoLtdCollaborationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_OtsukaPharmaceuticalCoLtdCollaborationMember</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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<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_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</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_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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><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 );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_LicenseOfDonidalorsenMember</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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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForDonidalorsenMember">
<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;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentServicesForDonidalorsenMember</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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538765072">
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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>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2023</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_PtcTherapeuticsCollaborationMember', window );">PTC Therapeutics [Member]</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_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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</tr>
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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_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner', window );">Royalty percentage received on net sales of medicine</a></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 );">- 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>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner</td>
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<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_PtcTherapeuticsCollaborationMember</td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989527277552">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Sobi (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, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 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 class="nump">$ 787,647<span></span>
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<td class="nump">$ 587,367<span></span>
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<td class="nump">$ 810,456<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_TypeOfArrangementAxis=ions_SwedishOrphanBiovitrumABDistributionAgreementMember', window );">Sobi [Member]</a></td>
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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_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>
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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">$ 2,646<span></span>
</td>
<td class="nump">$ 4,004<span></span>
</td>
<td class="nump">$ 7,443<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_TypeOfArrangementAxis=ions_SwedishOrphanBiovitrumABDistributionAgreementMember', window );">Sobi [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>
</tr>
<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>
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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_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
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<td class="nump">1.00%<span></span>
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<td class="nump">1.00%<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>
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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>
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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_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">1.00%<span></span>
</td>
<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>
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<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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(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>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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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538528896">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Bicycle Therapeutics (Details) - Bicycle License Agreement [Member] - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="2">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 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 class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LockUpAgreementTermOfTradingRestriction', window );">Trading restriction period under lock up agreement</a></td>
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<td class="text">&#160;<span></span>
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<td class="nump">7.2<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">
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<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">
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<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">
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<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>
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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>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_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/2003/role/disclosureRef<br> -Topic 730<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482916/730-10-50-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 912<br> -SubTopic 730<br> -Name Accounting Standards Codification<br> -Section 25<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482517/912-730-25-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 985<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481283/985-20-50-1<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;">us-gaap_ResearchAndDevelopmentExpense</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>
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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_TypeOfArrangementAxis=ions_BicycleCollaborationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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;">us-gaap_TypeOfArrangementAxis=ions_BicycleCollaborationMember</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>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538354352">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Metagenomi (Details) - Metagenomi [Member]<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </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>
</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="nump">4<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_NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized', window );">Number of additional targets to be researched, developed and commercialized | Target</a></td>
<td class="nump">4<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_PaymentToLicenseTechnology', window );">Payment to license technology | $</a></td>
<td class="nump">$ 80<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_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost', window );">Research and development expense | $</a></td>
<td class="nump">$ 80<span></span>
</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;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</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>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>
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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><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>
<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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<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_ions_PaymentToLicenseTechnology">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 technology 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_PaymentToLicenseTechnology</td>
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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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<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>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://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 730<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482916/730-10-50-1<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;">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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_MetagenomiLicenseAgreementMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_MetagenomiLicenseAgreementMember</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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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989540929568">
<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="4">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2023 </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 ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2015 </div>
<div>Program </div>
<div>Target</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 787,647<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<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>
</tr>
<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>
</tr>
<tr class="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">479,056<span></span>
</td>
<td class="nump">284,009<span></span>
</td>
<td class="nump">$ 468,061<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>
</tr>
<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>
</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="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="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="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="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_ContractWithCustomerLiability', window );">Deferred revenue</a></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>
</tr>
<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>
</tr>
<tr class="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">4.00%<span></span>
</td>
<td class="nump">4.00%<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_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>
</tr>
<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>
</tr>
<tr class="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">$ 28,426<span></span>
</td>
<td class="nump">$ 21,389<span></span>
</td>
<td class="nump">$ 0<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_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>
</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_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>
</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_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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>
</table>
<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>
</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_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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-21<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482907/825-10-50-20<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-18<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482861/275-10-50-20<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-8<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479837/606-10-45-2<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;">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> -Topic 924<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479941/924-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-5<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 42<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-42<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 40<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-40<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-41<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479806/606-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_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>
</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>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>87
<FILENAME>R58.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">
							function toggleNextSibling (e) {
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							e.nextSibling.style.display='block';
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</head>
<body>
<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989544396704">
<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, 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_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">68.00%<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">24.00%<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">8.00%<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">92.00%<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>
</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_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>
</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_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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>
</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_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>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>88
<FILENAME>R59.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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</head>
<body>
<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989537242896">
<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, 2023 </div>
<div>USD ($) </div>
<div>Company</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</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_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">7<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 Debt 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">$ 1,316,219<span></span>
</td>
<td class="nump">$ 1,223,522<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">415<span></span>
</td>
<td class="nump">64<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">(5,238)<span></span>
</td>
<td class="num">(12,018)<span></span>
</td>
</tr>
<tr class="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">1,311,396<span></span>
</td>
<td class="nump">1,211,568<span></span>
</td>
</tr>
<tr class="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 Debt 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">651,628<span></span>
</td>
<td class="nump">525,314<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">3,063<span></span>
</td>
<td class="nump">130<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">(1,197)<span></span>
</td>
<td class="num">(15,621)<span></span>
</td>
</tr>
<tr class="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">653,494<span></span>
</td>
<td class="nump">509,823<span></span>
</td>
</tr>
<tr class="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 Debt 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">1,967,847<span></span>
</td>
<td class="nump">1,748,836<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">3,478<span></span>
</td>
<td class="nump">194<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">(6,435)<span></span>
</td>
<td class="num">(27,639)<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">1,964,890<span></span>
</td>
<td class="nump">1,721,391<span></span>
</td>
</tr>
<tr class="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">35,012<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">25,237<span></span>
</td>
<td class="nump">17,257<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">(10,957)<span></span>
</td>
<td class="num">(1,358)<span></span>
</td>
</tr>
<tr class="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">49,292<span></span>
</td>
<td class="nump">50,911<span></span>
</td>
</tr>
<tr class="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 Debt 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">2,002,859<span></span>
</td>
<td class="nump">1,783,848<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">28,715<span></span>
</td>
<td class="nump">17,451<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">(17,392)<span></span>
</td>
<td class="num">(28,997)<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">2,014,182<span></span>
</td>
<td class="nump">1,772,302<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 Debt 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">559,967<span></span>
</td>
<td class="nump">513,790<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">157<span></span>
</td>
<td class="nump">23<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">(2,625)<span></span>
</td>
<td class="num">(4,365)<span></span>
</td>
</tr>
<tr class="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">557,499<span></span>
</td>
<td class="nump">509,448<span></span>
</td>
</tr>
<tr class="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 Debt 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">243,151<span></span>
</td>
<td class="nump">227,631<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">1,270<span></span>
</td>
<td class="nump">14<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">(692)<span></span>
</td>
<td class="num">(10,143)<span></span>
</td>
</tr>
<tr class="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">243,729<span></span>
</td>
<td class="nump">217,502<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 Debt 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">224,711<span></span>
</td>
<td class="nump">133,585<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">64<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_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(611)<span></span>
</td>
<td class="num">(1,829)<span></span>
</td>
</tr>
<tr class="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">224,164<span></span>
</td>
<td class="nump">131,756<span></span>
</td>
</tr>
<tr class="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 Debt 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">110,138<span></span>
</td>
<td class="nump">34,339<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">547<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">(21)<span></span>
</td>
<td class="num">(1,040)<span></span>
</td>
</tr>
<tr class="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">110,664<span></span>
</td>
<td class="nump">33,299<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 Debt 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">513,784<span></span>
</td>
<td class="nump">512,655<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">152<span></span>
</td>
<td class="nump">23<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">(1,889)<span></span>
</td>
<td class="num">(5,124)<span></span>
</td>
</tr>
<tr class="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">512,047<span></span>
</td>
<td class="nump">507,554<span></span>
</td>
</tr>
<tr class="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 Debt 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">294,873<span></span>
</td>
<td class="nump">245,030<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">1,239<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="num">(480)<span></span>
</td>
<td class="num">(4,109)<span></span>
</td>
</tr>
<tr class="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">295,632<span></span>
</td>
<td class="nump">240,921<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 Debt 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">17,757<span></span>
</td>
<td class="nump">57,484<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">42<span></span>
</td>
<td class="nump">18<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">(113)<span></span>
</td>
<td class="num">(686)<span></span>
</td>
</tr>
<tr class="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">17,686<span></span>
</td>
<td class="nump">56,816<span></span>
</td>
</tr>
<tr class="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 Debt 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">3,466<span></span>
</td>
<td class="nump">18,314<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">7<span></span>
</td>
<td class="nump">116<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">(4)<span></span>
</td>
<td class="num">(329)<span></span>
</td>
</tr>
<tr class="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">3,469<span></span>
</td>
<td class="nump">18,101<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 Debt 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="text">&#160;<span></span>
</td>
<td class="nump">6,008<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="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="num">(14)<span></span>
</td>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="nump">5,994<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="ro">
<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="re">
<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="ro">
<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">236<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_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(5,832)<span></span>
</td>
<td class="num">(1,358)<span></span>
</td>
</tr>
<tr class="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 );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">6,301<span></span>
</td>
<td class="nump">10,539<span></span>
</td>
</tr>
<tr class="re">
<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 Debt 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="ro">
<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 securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(4,200)<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="ro">
<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="re">
<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">23,115<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_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">25,001<span></span>
</td>
<td class="nump">17,257<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_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(5,125)<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_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">42,991<span></span>
</td>
<td class="nump">$ 40,372<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_InvestmentsDebtAndEquitySecuritiesAbstract', window );"><strong>Available-for-sale Debt 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="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedGain', window );">Unrealized gain on equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 2,600<span></span>
</td>
<td class="text">&#160;<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 publicly traded equity securities are included in other current
            assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2023, we recorded a $4.2 million net <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">unrealized loss in our consolidated statements of
              operations related to changes in the fair value of our investments in publicly traded companies.</span></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 privately held equity securities are included in deposits and other assets. We recognize our privately held 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, which are Level 3 inputs. In the year ended December 31, 2023<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we recorded a $</span>2.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million net unrealized gain in our consolidated statements of operations related to changes in the fair value of our investments in privately held companies.</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>
<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_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>
<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_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>
<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_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>
</table>
<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>
</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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-2<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;">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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-2<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;">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> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479130/326-30-45-1<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;">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> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-2<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481830/320-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479130/326-30-45-1<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;">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> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481830/320-10-45-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479130/326-30-45-1<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;">us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent</td>
</tr>
<tr>
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<td>us-gaap_</td>
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<tr>
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</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> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481830/320-10-45-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(12))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479130/326-30-45-1<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;">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>
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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>
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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_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> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479130/326-30-45-1<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;">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/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479130/326-30-45-1<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;">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>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_DebtSecuritiesCurrentAbstract</td>
</tr>
<tr>
<td style="padding-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_DebtSecuritiesNoncurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_DebtSecuritiesNoncurrentAbstract</td>
</tr>
<tr>
<td style="padding-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_EquitySecuritiesFVNIAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_EquitySecuritiesFVNIAbstract</td>
</tr>
<tr>
<td style="padding-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_EquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483467/210-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482736/825-10-45-1A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNi</td>
</tr>
<tr>
<td style="padding-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_EquitySecuritiesFvNiCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<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>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<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;">us-gaap_EquitySecuritiesFvNiCost</td>
</tr>
<tr>
<td style="padding-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_EquitySecuritiesFvNiUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 321<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479536/321-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNiUnrealizedGain</td>
</tr>
<tr>
<td style="padding-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_EquitySecuritiesFvNiUnrealizedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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> -Topic 321<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479536/321-10-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EquitySecuritiesFvNiUnrealizedLoss</td>
</tr>
<tr>
<td style="padding-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_InvestmentsAllOtherInvestmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_InvestmentsAllOtherInvestmentsAbstract</td>
</tr>
<tr>
<td style="padding-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_InvestmentsDebtAndEquitySecuritiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_InvestmentsDebtAndEquitySecuritiesAbstract</td>
</tr>
<tr>
<td style="padding-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_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember</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_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</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_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember</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_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember</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_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember</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_FinancialInstrumentAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember</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_FinancialInstrumentAxis=ions_EquitySecuritiesPrivateCompaniesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_FinancialInstrumentAxis=ions_EquitySecuritiesPrivateCompaniesMember</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>
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<SEQUENCE>89
<FILENAME>R60.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<html>
<head>
<title></title>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989539294624">
<tr>
<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, 2023 </div>
<div>USD ($) </div>
<div>Investment</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">455<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 857,398<span></span>
</td>
</tr>
<tr class="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">331,848<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">1,189,246<span></span>
</td>
</tr>
<tr class="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">(1,847)<span></span>
</td>
</tr>
<tr class="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">(4,588)<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">$ (6,435)<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">297<span></span>
</td>
</tr>
<tr class="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">$ 323,708<span></span>
</td>
</tr>
<tr class="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">178,183<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">501,891<span></span>
</td>
</tr>
<tr class="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">(553)<span></span>
</td>
</tr>
<tr class="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">(2,764)<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">$ (3,317)<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">63<span></span>
</td>
</tr>
<tr class="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">$ 199,372<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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">14,777<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">214,149<span></span>
</td>
</tr>
<tr class="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">(246)<span></span>
</td>
</tr>
<tr class="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">(386)<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">$ (632)<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">34<span></span>
</td>
</tr>
<tr class="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">$ 325,966<span></span>
</td>
</tr>
<tr class="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">131,000<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">456,966<span></span>
</td>
</tr>
<tr class="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">(1,031)<span></span>
</td>
</tr>
<tr class="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">(1,338)<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">$ (2,369)<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">61<span></span>
</td>
</tr>
<tr class="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">$ 8,352<span></span>
</td>
</tr>
<tr class="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">7,888<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">16,240<span></span>
</td>
</tr>
<tr class="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">(17)<span></span>
</td>
</tr>
<tr class="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">(100)<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">$ (117)<span></span>
</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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesAbstract</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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract</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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract</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 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/exampleRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479081/326-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-7<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479106/326-30-50-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger</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>
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<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
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<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>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://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-7<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479106/326-30-50-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss</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>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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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), 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/exampleRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479081/326-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-7<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479106/326-30-50-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months</td>
</tr>
<tr>
<td 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>debit</td>
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<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>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://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-7<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479106/326-30-50-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss</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>
<td>debit</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>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> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479106/326-30-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions</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>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/exampleRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479081/326-30-55-8<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-6<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479106/326-30-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition</td>
</tr>
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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>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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</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>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>
<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/otherTransitionRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-6<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479106/326-30-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss</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>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_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember">
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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_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember</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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<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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</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 );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember</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>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<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>
<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_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember</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> Balance Type:</strong></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_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember</td>
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<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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<DOCUMENT>
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<SEQUENCE>90
<FILENAME>R61.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989536758832">
<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, 2023</div></th>
<th class="th" colspan="2"><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, 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">$ 1,964,890<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 1,721,391<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">$ 49,292<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 50,911<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_ConvertibleSeniorNotes175PercentMember', window );">1.75% 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">1.75%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.75%<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="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">0.125%<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="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_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="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">0.00%<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>
</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="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">$ 6,301<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 10,539<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]</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">185,424<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">211,655<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">2,156,615<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,943,585<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="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">801,228<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">726,950<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</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="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">33,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">11,000<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>
</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="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">334,828<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">165,055<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="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">807,679<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">748,475<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="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">21,155<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">74,917<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 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="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="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">5,994<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] | Publicly Traded Equity Securities [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>[5]</sup></td>
<td class="nump">6,301<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">10,539<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">185,424<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">211,655<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">999,404<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">970,669<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="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 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="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 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="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">807,679<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">748,475<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="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] | 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="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="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="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] | Publicly Traded Equity Securities [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></sup></td>
<td class="nump">6,301<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">10,539<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">1,157,211<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">972,916<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] | 1.75% 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 );">Convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">661,100<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="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="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 );">Convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">42,400<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="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 );">Convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">667,800<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] | 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">801,228<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">726,950<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">334,828<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">165,055<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">
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<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">21,155<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">74,917<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="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">5,994<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] | Publicly Traded Equity Securities [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>
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<tr><td colspan="8"></td></tr>
<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">$33.0 million was included in cash and cash equivalents, 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">[3]</td>
<td style="vertical-align: top;" valign="top">$11.0 million was included in cash and cash equivalents, 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 in our consolidated balance sheets.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[5]</td>
<td style="vertical-align: top;" valign="top">Included in other current assets in our consolidated balance sheets.</td>
</tr>
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<div style="display: none;">
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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>
<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> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482106/820-10-50-2<br></p></div>
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<tr>
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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> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481800/320-10-50-2<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 320<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481830/320-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 326<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479130/326-30-45-1<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">
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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>
<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>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> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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">
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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>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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483467/210-10-45-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 825<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1A<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482736/825-10-45-1A<br></p></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>
<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>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> -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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br></p></div>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>91
<FILENAME>R62.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
<title></title>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989540924528">
<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, 2023</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, 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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Liability related to sale of future royalties</a></td>
<td class="nump">$ 513,736<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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">178,969<span></span>
</td>
<td class="nump">186,156<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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">8,859<span></span>
</td>
<td class="nump">8,998<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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">33,714<span></span>
</td>
<td class="nump">7,295<span></span>
</td>
<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 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">1,922,943<span></span>
</td>
<td class="nump">1,369,195<span></span>
</td>
<td class="text">&#160;<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_LongTermObligationsCurrent', window );">Less: current portion</a></td>
<td class="num">(8,831)<span></span>
</td>
<td class="num">(7,535)<span></span>
</td>
<td class="text">&#160;<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_LongTermObligationsNoncurrent', window );">Total Long-Term Obligations</a></td>
<td class="nump">1,914,112<span></span>
</td>
<td class="nump">1,361,660<span></span>
</td>
<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_ConvertibleSeniorNotes175PercentMember', window );">1.75 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_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="re">
<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">$ 562,285<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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">1.75%<span></span>
</td>
<td class="nump">1.75%<span></span>
</td>
<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_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="re">
<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">$ 625,380<span></span>
</td>
<td class="nump">$ 622,242<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<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="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="ro">
<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="re">
<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">$ 0<span></span>
</td>
<td class="nump">$ 544,504<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">0.125%<span></span>
</td>
<td class="text">&#160;<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_LiabilityRelatedToSaleOfFutureRoyaltiesNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 the unamortized liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate 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_LiabilityRelatedToSaleOfFutureRoyaltiesNet</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_LongTermObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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>
</table>
<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>
</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_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> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16)(a)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<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;">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> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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_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> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16)(a)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<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;">us-gaap_LoansPayableToBank</td>
</tr>
<tr>
<td style="padding-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_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>
<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_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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479041/842-20-45-1<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;">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://www.xbrl.org/2003/role/exampleRef<br> -Topic 946<br> -SubTopic 830<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480167/946-830-55-12<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(12)(b)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(12)(b)(3))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(15))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(12)(b)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<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;">us-gaap_OtherLiabilities</td>
</tr>
<tr>
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<td><strong> Data Type:</strong></td>
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember</td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
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<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>92
<FILENAME>R63.htm
<DESCRIPTION>IDEA: XBRL 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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989537566976">
<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="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>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2023</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, 2019</div></th>
<th class="th"><div>Apr. 30, 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_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 senior notes</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">$ 61,967<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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 );">Gain (loss) on early retirement of debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">13,389<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(8,627)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="nump">20,061<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">136,620<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">89,752<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">6,330<span></span>
</td>
<td class="nump">5,373<span></span>
</td>
<td class="nump">4,958<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_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="nump">5,900<span></span>
</td>
<td class="nump">5,300<span></span>
</td>
<td class="nump">4,900<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_ConvertibleSeniorNotes175PercentMember', window );">1.75% 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">575,000<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_ProceedsFromConvertibleDebt', window );">Proceeds from issuance of convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">575,000<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_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">575,000<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_DeferredFinanceCostsNet', window );">Unamortized debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 12,700<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="re">
<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">Jun. 30,  2028<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">1.75%<span></span>
</td>
<td class="nump">1.75%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="nump">2.30%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="nump">$ 53.73<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">10.7<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>
</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_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="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_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember', window );">1.75% 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_ProceedsFromConvertibleDebt', window );">Proceeds from issuance of convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 488,200<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="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="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="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_ProceedsFromConvertibleDebt', window );">Proceeds from issuance of convertible senior notes</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">$ 632,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" 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="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="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="nump">$ 7,200<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_DebtInstrumentMaturityDate', window );">Maturity date</a></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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="text">&#160;<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_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">$ 57.84<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">$ 76.39<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="nump">10.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="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>
</tr>
<tr class="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="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>
</tr>
<tr class="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="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>
</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="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_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember', 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="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_ProceedsFromConvertibleDebt', window );">Proceeds from issuance of convertible senior 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">$ 319,000<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_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="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_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 504,400<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" 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">504,400<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_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">44,500<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_DeferredFinanceCostsNet', window );">Unamortized debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 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_DebtInstrumentMaturityDate', window );">Maturity date</a></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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="nump">0.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="nump">$ 83.28<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_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="nump">$ 123.38<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.5<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>
</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_CallSpread', window );">Cost of call spread</a></td>
<td class="text">&#160;<span></span>
</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">$ 52,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="nump">108,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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>
<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_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="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_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member] | Other Income [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_GainsLossesOnExtinguishmentOfDebt', window );">Gain (loss) on early retirement of debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 13,400<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_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="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>
<td class="nump">439,300<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="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>
<td class="nump">109,500<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_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible senior 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">$ 309,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="nump">$ 375,600<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</tr>
<tr class="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="text">&#160;<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>
</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>
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<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>
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<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/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1F<br> -Subparagraph (b)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1F<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482925/835-30-45-3<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<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;">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://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 5<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-5<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482900/835-30-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69B<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481568/470-20-55-69B<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69C<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481568/470-20-55-69C<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482925/835-30-45-2<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482949/835-30-55-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482900/835-30-50-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482925/835-30-45-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<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> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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>
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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_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/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 820<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482106/820-10-50-2<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(2))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482925/835-30-45-3<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1D<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481303/470-50-40-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481303/470-50-40-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-15<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 27<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-27<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_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> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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>
</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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-14<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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>
<td><strong> Period Type:</strong></td>
<td>duration</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_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> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<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>
<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_ConvertibleSeniorNotes175PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ConvertibleSeniorNotes175PercentMember</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>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>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ConvertibleSeniorNotes175PercentUsedToRepurchase0125PercentConvertibleSeniorNotesMember</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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<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_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>
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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 );">- 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_ConvertibleSeniorNotes0PercentUsedToPayRemainingBalanceOf1PercentConvertibleSeniorNotesMember</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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<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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<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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember</td>
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<td>na</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_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember</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_ConvertibleSeniorNotes1PercentMember</td>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>93
<FILENAME>R64.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
<title></title>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989534613952">
<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="1">1 Months Ended</th>
<th class="th" colspan="4">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Aug. 31, 2023 </div>
<div>USD ($) </div>
<div>Lot</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($) </div>
<div>Option</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </div>
<div>Agreement</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($) </div>
<div>Facility</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt', window );">Number of purchased facilities financed with mortgage debt | Facility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor', window );">Number of purchase and sale agreements entered into with real estate investor | Agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossOnDispositionOfAssets1', window );">Gain on sale of real estate assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (161)<span></span>
</td>
<td class="nump">$ 149,604<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_ProceedsFromSaleOfPropertyPlantAndEquipment', window );">Proceeds from sale of real estate assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">22<span></span>
</td>
<td class="nump">254,083<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_RepaymentsOfSecuredDebt', window );">Payment of mortgage debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 160<span></span>
</td>
<td class="nump">50,686<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_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>
</tr>
<tr class="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>
</tr>
<tr class="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</a></td>
<td class="text">&#160;<span></span>
</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">$ 60,400<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>
</tr>
<tr class="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>
</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_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan', window );">Period to make interest only payments on mortgage loan</a></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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">51,300<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>
</tr>
<tr class="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>
</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_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan', window );">Period to make interest only payments on mortgage loan</a></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>
<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>
</tr>
<tr class="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>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 79,400<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_DebtInstrumentInterestRateStatedPercentage', window );">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="text">&#160;<span></span>
</td>
<td class="nump">3.88%<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>
</tr>
<tr class="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>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 14,000<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_DebtInstrumentInterestRateStatedPercentage', window );">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="text">&#160;<span></span>
</td>
<td class="nump">4.20%<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="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>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor', window );">Number of lots of undeveloped land transferred to real estate investor | 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>
</tr>
<tr class="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">$ 263,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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 lease</a></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>
<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="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>
</tr>
<tr class="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">5 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>
</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>
</tr>
<tr class="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>
</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_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor', window );">Number of lots of undeveloped land transferred to real estate investor | 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>
</tr>
<tr class="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="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>
<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_NewResearchAndDevelopmentFacilityInCarlsbadCAMember', window );">New R&amp;D Facility in Carlsbad, CA [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_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>
</tr>
<tr class="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 lease</a></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>
<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="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>
</tr>
<tr class="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">5 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>
</tr>
</table>
<div style="display: none;">
<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_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 transferred to 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_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor</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_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> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482900/835-30-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69B<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481568/470-20-55-69B<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69C<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481568/470-20-55-69C<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482925/835-30-45-2<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482949/835-30-55-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1B<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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_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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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_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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-13<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<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> -Topic 230<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
</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_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>
<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_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>
</table>
<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>
</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>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_NewResearchAndDevelopmentFacilityInCarlsbadCAMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_NewResearchAndDevelopmentFacilityInCarlsbadCAMember</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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989544288832">
<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, 2023 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_MaturitiesOfLongTermDebtAbstract', window );"><strong>Debt Maturities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths', window );">2024</a></td>
<td class="nump">$ 55,298<span></span>
</td>
</tr>
<tr class="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 );">2025</a></td>
<td class="nump">10,657<span></span>
</td>
</tr>
<tr class="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 );">2026</a></td>
<td class="nump">643,157<span></span>
</td>
</tr>
<tr class="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 );">2027</a></td>
<td class="nump">10,509<span></span>
</td>
</tr>
<tr class="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 );">2028</a></td>
<td class="nump">580,277<span></span>
</td>
</tr>
<tr class="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">8,462<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">1,308,360<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_LongTermDebtCurrent', window );">Less: Current portion included in other current liabilities</a></td>
<td class="num">(157)<span></span>
</td>
</tr>
<tr class="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">(47,138)<span></span>
</td>
</tr>
<tr class="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">(20,061)<span></span>
</td>
</tr>
<tr class="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">$ 1,241,004<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://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482925/835-30-45-3<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1D<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(15)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<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;">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, after deduction of 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://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -SubTopic 10<br> -Topic 210<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69B<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481568/470-20-55-69B<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 69C<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481568/470-20-55-69C<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1D<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16)(a)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479440/944-210-S99-1<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479853/942-210-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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 deduction of unamortized premium (discount) and debt issuance cost, of long-term debt classified as current. 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481544/470-10-50-1<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1E<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td style="padding-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_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1E<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481544/470-10-50-1<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;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths</td>
</tr>
<tr>
<td style="padding-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_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1E<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481544/470-10-50-1<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;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive</td>
</tr>
<tr>
<td style="padding-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_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1E<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481544/470-10-50-1<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;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour</td>
</tr>
<tr>
<td style="padding-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>
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<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_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1E<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481544/470-10-50-1<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;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree</td>
</tr>
<tr>
<td style="padding-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>
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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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-1E<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -SubTopic 10<br> -Topic 470<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481544/470-10-50-1<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;">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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<td><strong> Balance Type:</strong></td>
<td>credit</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, after deduction of 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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_LongTermDebtNoncurrent</td>
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<td>instant</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_MaturitiesOfLongTermDebtAbstract</td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989537215968">
<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="1">1 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Aug. 31, 2023 </div>
<div>USD ($) </div>
<div>Lot</div>
</th>
<th class="th">
<div>Dec. 31, 2023 </div>
<div>USD ($) </div>
<div>Option</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>
</tr>
<tr class="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>
</tr>
<tr class="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="nump">$ 279,536<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">171,896<span></span>
</td>
<td class="nump">$ 181,544<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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 );">Operating lease liabilities</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 178,969<span></span>
</td>
<td class="nump">186,156<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">13 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_OperatingLeaseWeightedAverageDiscountRatePercent', window );">Weighted average discount rate</a></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="nump">$ 20,100<span></span>
</td>
<td class="nump">$ 4,000<span></span>
</td>
<td class="nump">$ 3,300<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>
</tr>
<tr class="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>
</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="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">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_CarlsbadOfficeSpaceMember', window );">Carlsbad 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>
</tr>
<tr class="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>
</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="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_CarlsbadWarehouseSpaceMember', window );">Carlsbad Warehouse 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>
</tr>
<tr class="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>
</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="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>
</tr>
<tr class="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>
</tr>
<tr class="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 lease</a></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="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">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="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_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor', window );">Number of lots of undeveloped land transferred to real estate investor | 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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ImpairmentOfLongLivedAssetsHeldForUse', window );">Impairment charge</a></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>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration', window );">Impairment, Long-Lived Asset, Held-for-Use, Statement of Income [Extensible Enumeration]</a></td>
<td class="text">Selling, General and Administrative Expense<span></span>
</td>
<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_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>
</tr>
<tr class="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>
</tr>
<tr class="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 lease</a></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="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">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">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>
</tr>
<tr class="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>
</tr>
<tr class="ro">
<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>
</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_LessorOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend sublease | Option</a></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="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>
</tr>
<tr class="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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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 lease</a></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="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">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">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="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_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_LessorOperatingLeaseNumberOfOptionsToExtendLease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 lessor'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_LessorOperatingLeaseNumberOfOptionsToExtendLease</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_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_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 transferred to 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_NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor</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_us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 income or comprehensive income that includes impairment of long-lived asset held for 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> -Topic 360<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482099/360-10-50-2<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;">us-gaap_ImpairmentLongLivedAssetHeldForUseStatementOfIncomeOrComprehensiveIncomeExtensibleEnumeration</td>
</tr>
<tr>
<td style="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>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_ImpairmentOfLongLivedAssetsHeldForUse">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 amount of write-downs for impairments recognized during the period for long lived assets held for use (including those held for disposal by means other than 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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 360<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482099/360-10-50-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482130/360-10-45-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ImpairmentOfLongLivedAssetsHeldForUse</td>
</tr>
<tr>
<td style="padding-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_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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479773/842-30-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479773/842-30-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479041/842-20-45-1<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;">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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 5<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479041/842-20-45-5<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479041/842-20-45-1<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;">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/exampleRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 53<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479589/842-20-55-53<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 53<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479589/842-20-55-53<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
</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_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>
</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_CarlsbadOfficeSpaceMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_CarlsbadOfficeSpaceMember</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_CarlsbadWarehouseSpaceMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_CarlsbadWarehouseSpaceMember</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_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>
</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_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>
</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_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>
<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_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>
</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_AnotherOfficeSpaceInBostonMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_AnotherOfficeSpaceInBostonMember</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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<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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989534656992">
<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, 2023</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_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 );">2024</a></td>
<td class="nump">$ 20,398<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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 );">2025</a></td>
<td class="nump">20,645<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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 );">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="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 );">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="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 );">2028</a></td>
<td class="nump">20,774<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">176,138<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">279,536<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">(100,567)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">(8,094)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 170,875<span></span>
</td>
<td class="nump">$ 178,941<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 23,100<span></span>
</td>
<td class="nump">$ 8,300<span></span>
</td>
<td class="nump">$ 3,400<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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
</table>
<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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147478964/842-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 4<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479041/842-20-45-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<td><strong> Balance Type:</strong></td>
<td>debit</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_OperatingLeaseLiabilitiesPaymentsDueAbstract">
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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_OperatingLeaseLiabilitiesPaymentsDueAbstract</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>
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<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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479041/842-20-45-1<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;">us-gaap_OperatingLeaseLiabilityCurrent</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>
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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>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_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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479041/842-20-45-2<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;">us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList</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>enum2:enumerationSetItemType</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>instant</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_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> -Topic 842<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479041/842-20-45-1<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;">us-gaap_OperatingLeaseLiabilityNoncurrent</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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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>instant</td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989535685920">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Royalty Revenue Monetization (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Jan. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2023</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_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [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 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">$ 500,000<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_MaximumAmountOfPaymentsReceivableForAdditionalMilestones', window );">Maximum amount of payments receivable for additional milestones</a></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>
</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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Transaction costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,434<span></span>
</td>
<td class="nump">$ 29<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_ProceedsFromSaleOfFutureRoyalties', window );">Proceeds from sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">500,000<span></span>
</td>
<td class="nump">0<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_RoyaltyPayments', window );">Royalty payments to Royalty Pharma</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(44,628)<span></span>
</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_InterestExpenseRelatedToSaleOfFutureRoyalties', window );">Interest expense related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">68,238<span></span>
</td>
<td class="nump">0<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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Issuance costs related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(10,434)<span></span>
</td>
<td class="num">(29)<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_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Net liability related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">513,736<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_srt_ProductOrServiceAxis=ions_SpinrazaMember', window );">SPINRAZA [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="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>
<td class="text">&#160;<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_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid', window );">Maximum amount of annual sales on which royalty payments are paid</a></td>
<td class="nump">$ 1,500,000<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="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]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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>
<td class="text">&#160;<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 on annual sales of medicine</a></td>
<td class="nump">25.00%<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>
</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">$ 475,000<span></span>
</td>
<td class="nump">$ 475,000<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_srt_ProductOrServiceAxis=ions_SpinrazaMember', 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>
</tr>
<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>
<td class="text">&#160;<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 on annual sales of medicine</a></td>
<td class="nump">45.00%<span></span>
</td>
<td class="nump">45.00%<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_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="nump">$ 550,000<span></span>
</td>
<td class="nump">$ 550,000<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_srt_ProductOrServiceAxis=ions_PelacarsenMember', window );">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>
</tr>
<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>
<td class="text">&#160;<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 on annual sales of medicine</a></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>
</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_RoyaltyPurchaseAgreementMember', window );">Royalty Purchase Agreement [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="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>
<td class="text">&#160;<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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Transaction costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,434<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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="nump">13.50%<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_ProceedsFromSaleOfFutureRoyalties', window );">Proceeds from sale of future royalties</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>
</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_RoyaltyPayments', window );">Royalty payments to Royalty Pharma</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(44,628)<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_InterestExpenseRelatedToSaleOfFutureRoyalties', window );">Interest expense related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">68,238<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_LiabilityRelatedToSaleOfFutureRoyaltiesGross', window );">Liability related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">523,610<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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties', window );">Issuance costs related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(10,434)<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_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties', window );">Amortization of issuance costs related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">560<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_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Net liability related to sale of future royalties</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 513,736<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_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 the sale of future royalties.</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_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties</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_InterestExpenseRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 expense using the effective interest rate method related to the sale of future royalties.</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_InterestExpenseRelatedToSaleOfFutureRoyalties</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_LiabilityRelatedToSaleOfFutureRoyaltiesGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 amortization, of the liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate 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_LiabilityRelatedToSaleOfFutureRoyaltiesGross</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_LiabilityRelatedToSaleOfFutureRoyaltiesNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 the unamortized liability related to the sale of future royalties, pursuant to a royalty purchase agreement, that the Company is entitled to receive under collaboration agreements with Biogen and Novartis. The balance will be amortized over the estimated life of the arrangement using the effective interest rate 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_LiabilityRelatedToSaleOfFutureRoyaltiesNet</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_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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 for transaction costs 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_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties</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_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_ProceedsFromSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 future royalties under a 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_ProceedsFromSaleOfFutureRoyalties</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_RoyaltyPayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 royalty payments made during the period under a 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_RoyaltyPayments</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_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>
</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_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>
</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_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> -Topic 835<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482900/835-30-50-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482925/835-30-45-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<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> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481139/470-20-50-6<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989538795008">
<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, 2023</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_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">144,340,526<span></span>
</td>
<td class="nump">142,057,736<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">144,340,526<span></span>
</td>
<td class="nump">142,057,736<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 49,442<span></span>
</td>
<td class="nump">$ 6,373<span></span>
</td>
<td class="nump">$ 11,565<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_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">144,300,000<span></span>
</td>
<td class="nump">142,100,000<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">144,300,000<span></span>
</td>
<td class="nump">142,100,000<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">49,700,000<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">2,300,000<span></span>
</td>
<td class="nump">1,200,000<span></span>
</td>
<td class="nump">1,100,000<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">$ 49,400<span></span>
</td>
<td class="nump">$ 6,400<span></span>
</td>
<td class="nump">$ 11,600<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> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.29)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockNumberOfSharesParValueAndOtherDisclosuresAbstract">
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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_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>
<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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_CommonStockSharesIssued</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: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>
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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 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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481112/505-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.6-05(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-2<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-3<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(7))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-3<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_CommonStockSharesOutstanding</td>
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<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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
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<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td>na</td>
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<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 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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_PreferredStockSharesAuthorized</td>
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<td><strong> Balance Type:</strong></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 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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 13<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481112/505-10-50-13<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_PreferredStockSharesIssued</td>
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<td><strong> Balance Type:</strong></td>
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<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_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://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.6-05(4))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-2<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(4)(b))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-3<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.6-04(16)(a))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479617/946-210-S99-1<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 946<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.6-09(7))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483575/946-220-S99-3<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_PreferredStockSharesOutstanding</td>
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<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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-14<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 718<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2A<br></p></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_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions</td>
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<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>
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<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="12">12 Months Ended</th>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">14,091,000<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="nump">14,970,000<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" 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="nump">9,703,000<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">68,000<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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">35,200,000<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="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="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</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_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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</tr>
<tr class="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="nump">12,800,000<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">8,700,000<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">8,000,000<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Number of executive officers terminated before change in control when vesting will accelerate for executive officers | Officer</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Period before change in control when vesting will accelerate for executive officers</a></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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Period after change in control when vesting will accelerate for executive officers</a></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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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>
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</td>
</tr>
<tr class="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>
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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_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</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>
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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_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>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">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>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</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>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
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</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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">3,300,000<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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>
</tr>
<tr class="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="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
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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_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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</td>
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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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
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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_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">7 years<span></span>
</td>
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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_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member] | Stock Options [Member] | Issued after December 31, 2021 [Member]</a></td>
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</td>
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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_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
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</td>
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</td>
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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_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">10 years<span></span>
</td>
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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_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>
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</td>
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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_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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</td>
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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_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">25.00%<span></span>
</td>
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</td>
</tr>
<tr class="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">1 year<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</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>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
</tr>
<tr class="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>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="nump">200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
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</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="text">&#160;<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</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="re">
<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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod', window );">Holding period for purchased stock</a></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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="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>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased', window );">Weighted average purchase price (in dollars per share) | $ / shares</a></td>
<td class="nump">$ 30.53<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_EmployeeStockPurchasePlanSharesAvailableForPurchase', window );">Shares available for purchase under ESPP (in shares)</a></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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -SubTopic 10<br> -Topic 718<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -SubTopic 10<br> -Topic 718<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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_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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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>
</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_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481112/505-10-50-2<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480008/505-10-S99-1<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">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>
</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>
</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>
</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_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_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_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_PlanNameAxis=ions_NonemployeeDirectorsStockOptionPlan2002Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_NonemployeeDirectorsStockOptionPlan2002Member</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_EmployeeStockPurchasePlanMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_EmployeeStockPurchasePlanMember</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>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>100
<FILENAME>R71.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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989534822848">
<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, 2023</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_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">14,970<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">2,407<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">(1,444)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">(1,842)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">14,091<span></span>
</td>
<td class="nump">14,970<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">9,703<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 50.57<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">38.8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">45.06<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">55.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">48.43<span></span>
</td>
<td class="nump">$ 50.57<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 52.24<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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 8 months 26 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">3 years 2 months 12 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">$ 78,542<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 28,349<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 19.72<span></span>
</td>
<td class="nump">$ 18.66<span></span>
</td>
<td class="nump">$ 24.35<span></span>
</td>
</tr>
<tr class="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">$ 6,000<span></span>
</td>
<td class="nump">$ 1,400<span></span>
</td>
<td class="nump">$ 2,500<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">$ 65,100<span></span>
</td>
<td class="nump">$ 3,600<span></span>
</td>
<td class="nump">$ 8,500<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue', window );">Weighted-average fair value of options exercised (in dollars per share)</a></td>
<td class="nump">$ 49.23<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 36,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-14<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 718<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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">
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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>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>
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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>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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice</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>dtr-types:perShareItemType</td>
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<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_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>
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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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<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_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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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>
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<td><strong> Period Type:</strong></td>
<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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(03)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice</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>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>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_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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1</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>xbrli:monetaryItemType</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>
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<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> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1</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:durationItemType</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>
</tr>
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<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> -Topic 718<br> -SubTopic 10<br> -Subparagraph (e)(1)<br> -Name Accounting Standards Codification<br> -Paragraph 2<br> -Section 50<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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>
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<tr>
<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_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://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -SubTopic 10<br> -Topic 505<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481112/505-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 505<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480008/505-10-S99-1<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480566/210-10-S99-1<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;">us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised</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>duration</td>
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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>
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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_AwardTypeAxis=us-gaap_StockOptionMember</td>
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<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989536551696">
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<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>
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<tr>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</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_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward', window );"><strong>Number of Shares [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at beginning of period (in shares)</a></td>
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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_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod', window );">Granted (in shares)</a></td>
<td class="nump">1,707<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="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">(1,055)<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">(179)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">3,239<span></span>
</td>
<td class="nump">2,766<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 48.3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">40.51<span></span>
</td>
<td class="nump">$ 36.14<span></span>
</td>
<td class="nump">$ 57.02<span></span>
</td>
</tr>
<tr class="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">51.64<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">42.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" 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">$ 43.4<span></span>
</td>
<td class="nump">$ 48.3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 53.7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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 3 months 18 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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(03)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(03)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue</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:perShareItemType</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>
</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_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward</td>
</tr>
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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: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>
</tr>
</table></div>
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<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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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>
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<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>
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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>
<td>na</td>
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<td></td>
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<head>
<title></title>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989544033888">
<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, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</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_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>
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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_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at beginning of period (in shares)</a></td>
<td class="nump">143<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">158<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">(75)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<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">226<span></span>
</td>
<td class="nump">143<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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="re">
<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">$ 52.59<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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">57.43<span></span>
</td>
<td class="nump">$ 42.28<span></span>
</td>
<td class="nump">$ 77.17<span></span>
</td>
</tr>
<tr class="re">
<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">52.43<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 56.04<span></span>
</td>
<td class="nump">$ 52.59<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">$ 4.4<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 4 months 24 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>
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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>
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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_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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</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>
<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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">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><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>instant</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 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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod</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>
</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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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue</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 );">- 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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber</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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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward">
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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>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>
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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>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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue</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_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward</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>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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod</td>
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<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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue</td>
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<tr>
<td><strong> Name:</strong></td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989544178176">
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<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>
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<tr>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
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<td class="nump">$ 120,678<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">499<span></span>
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<td class="nump">533<span></span>
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<td class="nump">456<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">73,704<span></span>
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<td class="nump">87,522<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_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation [Abstract]</strong></a></td>
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<td class="nump">$ 26,027<span></span>
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<td class="nump">$ 32,700<span></span>
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<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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.F)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479830/718-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (h)(1)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<br></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;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989534806096">
<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, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</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_EmployeeStockOptionMember', window );">Employee 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>
</tr>
<tr class="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>
</tr>
<tr class="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">3.80%<span></span>
</td>
<td class="nump">2.10%<span></span>
</td>
<td class="nump">0.60%<span></span>
</td>
</tr>
<tr class="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>
</td>
</tr>
<tr class="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">46.80%<span></span>
</td>
<td class="nump">54.50%<span></span>
</td>
<td class="nump">54.00%<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_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">6 years 3 months 18 days<span></span>
</td>
<td class="text">6 years 3 months 18 days<span></span>
</td>
<td class="text">4 years 10 months 24 days<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 );">Employee Stock Options [Member] | 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>
</tr>
<tr class="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>
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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_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">7 years<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_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>
</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>
</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_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">10 years<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_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member] | 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>
</tr>
<tr class="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_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">7 years<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_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>
</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_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>
</tr>
<tr class="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>
<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_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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<tr class="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">3.80%<span></span>
</td>
<td class="nump">2.90%<span></span>
</td>
<td class="nump">1.20%<span></span>
</td>
</tr>
<tr class="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>
</td>
</tr>
<tr class="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">52.70%<span></span>
</td>
<td class="nump">56.20%<span></span>
</td>
<td class="nump">55.90%<span></span>
</td>
</tr>
<tr class="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 8 months 12 days<span></span>
</td>
<td class="text">7 years 4 months 24 days<span></span>
</td>
<td class="text">7 years 3 months 18 days<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_AwardTypeAxis=us-gaap_EmployeeStockMember', window );">ESPP [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_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>
</tr>
<tr class="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">5.30%<span></span>
</td>
<td class="nump">1.20%<span></span>
</td>
<td class="nump">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_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>
</td>
</tr>
<tr class="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">36.00%<span></span>
</td>
<td class="nump">50.10%<span></span>
</td>
<td class="nump">42.40%<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_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>
</tr>
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<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>
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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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<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>
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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 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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate</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>dtr-types:percentItemType</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 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>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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iv)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate</td>
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<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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate</td>
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<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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod</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>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> -Topic 718<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(i)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480429/718-10-50-2<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;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1</td>
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<td><strong> Name:</strong></td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989544145056">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, 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, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</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_IncomeTaxDisclosureAbstract', window );"><strong>Income Taxes [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="num">$ (334,707)<span></span>
</td>
<td class="num">$ (258,493)<span></span>
</td>
<td class="num">$ (29,966)<span></span>
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<td class="nump">742<span></span>
</td>
<td class="nump">508<span></span>
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<td class="nump">818<span></span>
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<td class="num">$ (333,965)<span></span>
</td>
<td class="num">$ (257,985)<span></span>
</td>
<td class="num">$ (29,148)<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 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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic</td>
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<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>
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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_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest</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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<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>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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">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>
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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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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxDisclosureAbstract">
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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_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>
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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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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989545001504">
<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, 2023</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_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">$ 35,861<span></span>
</td>
<td class="nump">$ 10,522<span></span>
</td>
<td class="num">$ (200)<span></span>
</td>
</tr>
<tr class="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="num">(3,687)<span></span>
</td>
<td class="nump">1,129<span></span>
</td>
<td class="num">(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_CurrentForeignTaxExpenseBenefit', window );">Foreign</a></td>
<td class="nump">147<span></span>
</td>
<td class="nump">86<span></span>
</td>
<td class="nump">339<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">32,321<span></span>
</td>
<td class="nump">11,737<span></span>
</td>
<td class="num">(551)<span></span>
</td>
</tr>
<tr class="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">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_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">0<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">$ 32,321<span></span>
</td>
<td class="nump">$ 11,737<span></span>
</td>
<td class="num">$ (551)<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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-9<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">us-gaap_CurrentFederalTaxExpenseBenefit</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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<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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-9<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-9<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td style="padding-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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<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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-9<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">us-gaap_CurrentStateAndLocalTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-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_DeferredFederalIncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-9<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">us-gaap_DeferredFederalIncomeTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-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_DeferredIncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 230<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482740/230-10-45-28<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-9<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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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<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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<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_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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<tr>
<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>
</div></td></tr>
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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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-9<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">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>
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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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</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_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> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-8<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-9<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-10<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -SubTopic 20<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482659/740-20-45-2<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -SubTopic 10<br> -Topic 235<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<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;">us-gaap_IncomeTaxExpenseBenefit</td>
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<td>xbrli:monetaryItemType</td>
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<td>debit</td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989527290448">
<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, 2023</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_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">$ (333,965)<span></span>
</td>
<td class="num">$ (257,985)<span></span>
</td>
<td class="num">$ (29,148)<span></span>
</td>
</tr>
<tr class="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">(70,133)<span></span>
</td>
<td class="num">(54,177)<span></span>
</td>
<td class="num">(6,121)<span></span>
</td>
</tr>
<tr class="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">(22,597)<span></span>
</td>
<td class="num">(13,622)<span></span>
</td>
<td class="nump">4,278<span></span>
</td>
</tr>
<tr class="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">(22)<span></span>
</td>
<td class="num">(49)<span></span>
</td>
<td class="nump">143<span></span>
</td>
</tr>
<tr class="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">175,388<span></span>
</td>
<td class="nump">104,951<span></span>
</td>
<td class="nump">2,885<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">0<span></span>
</td>
<td class="nump">262<span></span>
</td>
</tr>
<tr class="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">(67,131)<span></span>
</td>
<td class="num">(39,729)<span></span>
</td>
<td class="num">(23,198)<span></span>
</td>
</tr>
<tr class="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="nump">4<span></span>
</td>
<td class="num">(20)<span></span>
</td>
<td class="num">(24)<span></span>
</td>
</tr>
<tr class="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="nump">1,023<span></span>
</td>
<td class="num">(3,091)<span></span>
</td>
<td class="nump">12,838<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">3,814<span></span>
</td>
<td class="nump">3,023<span></span>
</td>
<td class="nump">5,085<span></span>
</td>
</tr>
<tr class="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">327<span></span>
</td>
<td class="nump">57<span></span>
</td>
<td class="nump">84<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount', window );">Foreign-derived intangible income benefit</a></td>
<td class="num">(7,493)<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_IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost', window );">Stock-based compensation</a></td>
<td class="nump">19,546<span></span>
</td>
<td class="nump">14,030<span></span>
</td>
<td class="nump">4,720<span></span>
</td>
</tr>
<tr class="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="num">(405)<span></span>
</td>
<td class="nump">364<span></span>
</td>
<td class="num">(1,503)<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">$ 32,321<span></span>
</td>
<td class="nump">$ 11,737<span></span>
</td>
<td class="num">$ (551)<span></span>
</td>
</tr>
<tr class="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">6.80%<span></span>
</td>
<td class="nump">5.30%<span></span>
</td>
<td class="num">(14.70%)<span></span>
</td>
</tr>
<tr class="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="nump">0.00%<span></span>
</td>
<td class="num">(0.50%)<span></span>
</td>
</tr>
<tr class="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">(52.50%)<span></span>
</td>
<td class="num">(40.70%)<span></span>
</td>
<td class="num">(9.90%)<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="nump">0.00%<span></span>
</td>
<td class="num">(0.90%)<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_EffectiveIncomeTaxRateReconciliationTaxCredits', window );">Tax credits</a></td>
<td class="nump">20.10%<span></span>
</td>
<td class="nump">15.40%<span></span>
</td>
<td class="nump">79.60%<span></span>
</td>
</tr>
<tr class="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">0.00%<span></span>
</td>
<td class="nump">0.10%<span></span>
</td>
</tr>
<tr class="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="num">(0.30%)<span></span>
</td>
<td class="nump">1.20%<span></span>
</td>
<td class="num">(44.00%)<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_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent', window );">Non-deductible compensation</a></td>
<td class="num">(1.10%)<span></span>
</td>
<td class="num">(1.20%)<span></span>
</td>
<td class="num">(17.40%)<span></span>
</td>
</tr>
<tr class="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="num">(0.10%)<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="num">(0.30%)<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_EffectiveIncomeTaxRateReconciliationFdiiPercent', window );">Foreign-derived intangible income benefit</a></td>
<td class="nump">2.20%<span></span>
</td>
<td class="nump">0.00%<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_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost', window );">Stock-based compensation</a></td>
<td class="num">(5.90%)<span></span>
</td>
<td class="num">(5.40%)<span></span>
</td>
<td class="num">(16.20%)<span></span>
</td>
</tr>
<tr class="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="nump">0.10%<span></span>
</td>
<td class="num">(0.10%)<span></span>
</td>
<td class="nump">5.10%<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">(9.70%)<span></span>
</td>
<td class="num">(4.50%)<span></span>
</td>
<td class="nump">1.90%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">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/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">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_EffectiveIncomeTaxRateReconciliationFdiiAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 benefit from difference to expected income tax expense (benefit) computed by applying domestic federal statutory income tax rate to pretax income (loss) from continuing operations, attributable to foreign-derived intangible income (FDII).</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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationFdiiAmount</td>
</tr>
<tr>
<td style="padding-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_EffectiveIncomeTaxRateReconciliationFdiiPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 reported income tax benefit from difference to income tax expense (benefit) computed by applying domestic federal statutory income tax rate to pretax income (loss) from continuing operations, attributable to foreign-derived intangible income (FDII).</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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationFdiiPercent</td>
</tr>
<tr>
<td style="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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments</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>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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<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;">us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits</td>
</tr>
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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: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> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(11))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 5: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 31<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-31<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 235<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479557/942-235-S99-1<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Section 25<br> -Paragraph 1<br> -SubTopic 20<br> -Topic 940<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147481913/940-20-25-1<br><br>Reference 9: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(10))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<br><br>Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(15))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483589/942-220-S99-1<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;">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> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-8<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-9<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-10<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.7)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147479360/740-10-S99-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -SubTopic 20<br> -Topic 740<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482659/740-20-45-2<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -SubTopic 10<br> -Topic 235<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-1<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;">us-gaap_IncomeTaxExpenseBenefit</td>
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<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>
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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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<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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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>
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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_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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 15<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482525/740-10-45-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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_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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989541146912">
<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, 2023</div></th>
<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_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">$ 77,964<span></span>
</td>
<td class="nump">$ 87,802<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_DeferredTaxAssetsTaxCreditCarryforwards', window );">Tax credits</a></td>
<td class="nump">239,962<span></span>
</td>
<td class="nump">277,436<span></span>
</td>
</tr>
<tr class="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">71,683<span></span>
</td>
<td class="nump">85,700<span></span>
</td>
</tr>
<tr class="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">77,468<span></span>
</td>
<td class="nump">86,983<span></span>
</td>
</tr>
<tr class="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">104,380<span></span>
</td>
<td class="nump">104,649<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">16,849<span></span>
</td>
<td class="nump">34,384<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_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses', window );">Capitalized research and development expenses</a></td>
<td class="nump">238,738<span></span>
</td>
<td class="nump">119,635<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_DeferredTaxAssetsLeasingArrangements', window );">Long-term lease liabilities</a></td>
<td class="nump">43,718<span></span>
</td>
<td class="nump">45,612<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_DeferredTaxAssetsSaleOfFutureRoyalties', window );">Sale of future royalties</a></td>
<td class="nump">144,608<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_DeferredTaxAssetsOther', window );">Other</a></td>
<td class="nump">10,343<span></span>
</td>
<td class="nump">15,813<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">1,025,713<span></span>
</td>
<td class="nump">858,014<span></span>
</td>
</tr>
<tr class="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">(4,166)<span></span>
</td>
<td class="num">(4,475)<span></span>
</td>
</tr>
<tr class="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">(42,007)<span></span>
</td>
<td class="num">(44,504)<span></span>
</td>
</tr>
<tr class="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">(1,910)<span></span>
</td>
<td class="num">(313)<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">977,630<span></span>
</td>
<td class="nump">808,722<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_DeferredTaxAssetsValuationAllowance', window );">Valuation allowance</a></td>
<td class="num">(977,630)<span></span>
</td>
<td class="num">(808,722)<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">$ 169,000<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_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_ions_DeferredTaxAssetsSaleOfFutureRoyalties">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 the sale of future royalties.</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_DeferredTaxAssetsSaleOfFutureRoyalties</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://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-6<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-2<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;">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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-2<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;">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://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-6<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-6<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-6<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-8<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-6<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-2<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;">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>
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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_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://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-6<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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>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_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://www.xbrl.org/2009/role/commonPracticeRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-6<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-6<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-8<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<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> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 4<br> -Subparagraph (SX 210.12-09)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480678/235-10-S99-4<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989534522416">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Tax Credit Carryforwards (Details)<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th">
<div>Dec. 31, 2023 </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>
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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_IncomeTaxAuthorityNameAxis=us-gaap_CaliforniaFranchiseTaxBoardMember', window );">California [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_OperatingLossCarryforwardsLineItems', window );"><strong>Operating Loss 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_OperatingLossCarryforwards', window );">Net operating loss carryforwards</a></td>
<td class="nump">398.8<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_TaxCreditCarryforwardAxis=us-gaap_ResearchMember', window );">Research and Development [Member] | 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_TaxCreditCarryforwardLineItems', window );"><strong>Tax Credit 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_TaxCreditCarryforwardAmount', window );">Tax credit carryforwards</a></td>
<td class="nump">169.7<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_TaxCreditCarryforwardAxis=us-gaap_ResearchMember', window );">Research and Development [Member] | California [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">124.4<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_IncomeTaxAuthorityAxis=us-gaap_StateAndLocalJurisdictionMember', window );">State [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 custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_OperatingLossCarryforwardsUtilized', window );">Operating loss carryforwards utilized</a></td>
<td class="nump">$ 3.2<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_OperatingLossCarryforwardsUtilized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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, utilized during the period to reduce taxable income.</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_OperatingLossCarryforwardsUtilized</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_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> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<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_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> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-3<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_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>
</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>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxAuthorityAxis=us-gaap_StateAndLocalJurisdictionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_IncomeTaxAuthorityAxis=us-gaap_StateAndLocalJurisdictionMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
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<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>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989534862112">
<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, 2023</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_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">$ 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_UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations', window );">Decrease for lapse of statute of limitations</a></td>
<td class="num">(14,993)<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_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions', window );">Decrease for prior period tax positions</a></td>
<td class="num">(737)<span></span>
</td>
<td class="num">(267)<span></span>
</td>
<td class="num">(695)<span></span>
</td>
</tr>
<tr class="re">
<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">429<span></span>
</td>
<td class="nump">259<span></span>
</td>
<td class="nump">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_UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions', window );">Increase for current period tax positions</a></td>
<td class="nump">2,032<span></span>
</td>
<td class="nump">1,490<span></span>
</td>
<td class="nump">1,354<span></span>
</td>
</tr>
<tr class="re">
<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">43,298<span></span>
</td>
<td class="nump">56,567<span></span>
</td>
<td class="nump">55,085<span></span>
</td>
</tr>
<tr class="ro">
<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">300<span></span>
</td>
<td class="nump">6,200<span></span>
</td>
<td class="nump">6,200<span></span>
</td>
</tr>
<tr class="re">
<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">7,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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">$ 100<span></span>
</td>
<td class="nump">$ 800<span></span>
</td>
<td class="nump">$ 500<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> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15<br> -Subparagraph (d)(3)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-15A<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10B<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482525/740-10-45-10B<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-15A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-15<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-15A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(1)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-15A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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_UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 lapses of applicable statutes of limitations.</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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-15A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsReductionsResultingFromLapseOfApplicableStatuteOfLimitations</td>
</tr>
<tr>
<td style="padding-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_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> -Topic 740<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482685/740-10-50-15A<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989541172640">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Employment Benefits (Details) - USD ($)<br></strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract', window );"><strong>Employee Benefits [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DefinedContributionPlanCostRecognized', window );">Matching contributions</a></td>
<td class="nump">$ 7,100,000<span></span>
</td>
<td class="nump">$ 5,600,000<span></span>
</td>
<td class="nump">$ 5,500,000<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_srt_RangeAxis=srt_MinimumMember', 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>
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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>
</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_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount', window );">Employee contribution limit per calendar year</a></td>
<td class="nump">22,500<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_RangeAxis=srt_MaximumMember', 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="re">
<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>
</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_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount', window );">Employee contribution limit per calendar year</a></td>
<td class="nump">$ 30,000<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_DefinedContributionPlanCostRecognized">
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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 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> -Topic 715<br> -SubTopic 70<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480794/715-70-50-1<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;">us-gaap_DefinedContributionPlanCostRecognized</td>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>debit</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>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">
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<td style="white-space:nowrap;">us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount</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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<td><strong> Name:</strong></td>
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<span style="display: none;">v3.24.0.1</span><table class="report" border="0" cellspacing="2" id="idm139989534411456">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fourth Quarter Financial Data (Unaudited) (Details) - USD ($)<br> $ / shares in Units, $ in Thousands</strong></div></th>
<th class="th" colspan="4">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
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<tr>
<th class="th" colspan="2"><div>Dec. 31, 2023</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2023</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_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>
</tr>
<tr class="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">$ 324,505<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 151,890<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_CostsAndExpenses', window );">Operating expenses</a></td>
<td class="nump">330,627<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">359,909<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 1,141,377<span></span>
</td>
<td class="nump">$ 997,558<span></span>
</td>
<td class="nump">$ 840,642<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">(6,122)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(208,019)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(353,730)<span></span>
</td>
<td class="num">(410,191)<span></span>
</td>
<td class="num">(30,186)<span></span>
</td>
</tr>
<tr class="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">$ (9,263)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (52,430)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="num">$ (366,286)<span></span>
</td>
<td class="num">$ (269,722)<span></span>
</td>
<td class="num">$ (28,597)<span></span>
</td>
</tr>
<tr class="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">$ (0.06)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4],[5]</sup></td>
<td class="num">$ (0.37)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4],[5]</sup></td>
<td class="num">$ (2.56)<span></span>
</td>
<td class="num">$ (1.9)<span></span>
</td>
<td class="num">$ (0.2)<span></span>
</td>
</tr>
<tr class="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 loss per share (in dollars per share)</a></td>
<td class="num">$ (0.06)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="num">$ (0.37)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4],[6]</sup></td>
<td class="num">$ (2.56)<span></span>
</td>
<td class="num">$ (1.9)<span></span>
</td>
<td class="num">$ (0.2)<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_SaleAndLeasebackTransactionGainLossNet', window );">Gain on sale of real estate assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 150,100<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (161)<span></span>
</td>
<td class="nump">$ 150,135<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_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember', window );">WAINUA (Eplontersen) [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>
</tr>
<tr class="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>
</tr>
<tr class="re">
<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">$ 50,000<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>
</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 [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>
</tr>
<tr class="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>
</tr>
<tr class="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">$ 36,000<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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="8"></td></tr>
<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">Revenue was higher in the three months ended December 31, 2023
            compared to the same period in 2022 primarily due to the $50 million milestone payment we earned from AstraZeneca when the FDA approved
            WAINUA for ATTRv-PN in the U.S., $36 million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth
            quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis.</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 lower in the three months ended December 31,
            2023 compared to the same period in 2022 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 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 loss per share by dividing the total net 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 incurred a net loss for the fourth quarter of 2023 and 2022. As a
            result, 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.</td>
</tr>
</table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostsAndExpenses">
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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>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> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<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>
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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 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> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-3<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 15<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482635/260-10-55-15<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 815<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480175/815-40-65-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 815<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147480175/815-40-65-1<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-11<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-11<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-7<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-2<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-60B<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483443/250-10-50-4<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482662/260-10-50-1<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-10<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483621/220-10-S99-2<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 942<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483589/942-220-S99-1<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 944<br> -SubTopic 220<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147483586/944-220-S99-1<br><br>Reference 16: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 55<br> -Paragraph 52<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482635/260-10-55-52<br><br>Reference 17: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 7<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482689/260-10-45-7<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>dtr-types:perShareItemType</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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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareDiluted">
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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 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>
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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_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_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_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>
<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> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 22<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-22<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-30<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 31<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-31<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 280<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org//1943274/2147482810/280-10-50-32<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><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>
<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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost">
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<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>
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<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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<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>
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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 quarter ended December 31, 2023, our
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&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;

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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Contract, instruction or written plan intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) under the Exchange Act.&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: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&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;"&gt;&#x201c;Non-Rule 10b5-1 trading arrangement&#x201d; as defined in item 408(c) of Regulation S-K under the Exchange Act.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

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


  &lt;tr&gt;

    &lt;td rowspan="2" style="width: 21.67%; vertical-align: bottom;"&gt; &lt;/td&gt;

    &lt;td rowspan="2" style="width: 2.45%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td rowspan="2" style="width: 9%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Action&lt;/div&gt;
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    &lt;td rowspan="2" style="width: 2.14%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td rowspan="2" style="width: 15.03%; vertical-align: bottom; border-bottom: #000000 2px solid;"&gt;
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    &lt;td rowspan="2" style="width: 2.26%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="3" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"&gt;
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    &lt;td rowspan="2" style="width: 2.14%; vertical-align: 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; to be Sold&lt;/div&gt;
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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,079&lt;/div&gt;
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    <us-gaap:OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTextBlock
      contextRef="c20230101to20231231"
      id="Text_ff0d474e98da4a028ee98216059cc7d3">
&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
    wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;).&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;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 United States, or
    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 WAINUA 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 selling, general and administrative, or SG&amp;amp;A, expense and research and development, or 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: 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&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&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&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&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&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&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 may 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. When a partner exercises its option to license a
      medicine that was not previously determined to be a material right at the inception of the agreement 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.&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&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 that 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&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&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&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&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&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&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&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 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&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&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&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&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&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;"&gt;We recognize royalty revenue 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;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 Swedish Orphan Biovitrum AB, or 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; 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&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&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&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&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&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 Note 4, &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: 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, 2023,
    approximately 87.8 percent of our contracts receivables were from one significant customer. As of December 31, 2022, approximately 82.5 percent of our contracts receivables were from one
    significant customer.&lt;/div&gt;

&lt;div&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;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, 2023 and 2022, we recognized $78.2 million and $73.5 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 R&amp;amp;D operations. We expense R&amp;amp;D costs as we incur them. When we make payments for R&amp;amp;D 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 R&amp;amp;D expenses are costs associated with our partner agreements. In 2023, 2022 and 2021, patent expenses were $4.3 million, $4.7 million and $5.3 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="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 our net loss by our weighted-average number of common shares outstanding during the
    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;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, 2023,
    2022 and 2021, 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 from 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&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;&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&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;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&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&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&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&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&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&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 year ended December 31, 2023, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, 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;div style="display:none;"&gt;&lt;br/&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, 2023, 2022 and 2021, we had warrants related to our 0% Notes and 0.125% 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&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 years ended
    December 31, 2023 and 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; 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 we 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 PRSUs we granted in 2020 through 2022, &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. These PRSU awards also included an alternative three-year payout mechanism, or the Alternative Calculation, under
    which we must calculate an alternative payout at the end of the final three-year measurement period assuming the only measurement period for all
    shares under the award was the three-year period. If the Alternative Calculation is greater than payouts under the sum of the three years, then such PRSU award will pay out to achieve the number of shares payable under the Alternative Calculation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 PRSUs we granted in 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period
    based on our relative TSR as compared to a peer group of companies and as measured at the end of the 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 200 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 Note 8, &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: 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&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="display:none;"&gt;&lt;br/&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="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 public and private biotechnology companies that we received as part
      of a technology license or partner agreement. At December 31, 2023, we held equity investments in three publicly traded companies and seven 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 publicly traded companies at their listed stock price. 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="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 we determine as the following (in years):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

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


  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt; &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Useful Lives&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;"&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 style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&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;/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;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;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, 2023, we
    had three outstanding convertible senior notes, our 1.75% Notes, which mature in June 2028, our 0% Notes, which mature in April 2026, and
    our 0.125% Notes, which mature in December 2024. Refer to Note 7, &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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Liability Related to Sale of Future 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;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 arrangements with Biogen and Novartis, respectively. Refer to Note 7, &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 the 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;Under our agreement with Royalty Pharma, we record upfront payments and milestone payments we receive from the sale of future royalties as
    a liability, net of transaction costs. We record royalty payments made to Royalty Pharma as a reduction of the liability or accrued interest and amortize the transaction costs over the estimated life of the royalty stream. We account for the associated
    interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the related product and recognizes the related 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 calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense using our
    current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material
    change in our estimate, we will prospectively adjust the effective interest rate and the related interest expense.&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;We operate 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.&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 Issued 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 November 2023, the Financial Accounting Standards Board, or FASB, issued updated guidance on segment reporting. The guidance requires
    public companies with a single reportable segment to provide all disclosures required under ASC 280, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Segment Reporting&lt;/span&gt;. In addition, the guidance
    requires public companies to include in interim reports all disclosures related to a reportable segment's profit or loss and assets that are currently required in annual reports. This update is effective for annual periods beginning after December 15,
    2023 and interim periods beginning after December 15, 2024. The guidance is applied on a retrospective basis for all periods presented in the financial statements, unless it is impracticable. Early adoption of this guidance is permitted. We currently
    plan to adopt the annual reporting requirements in our 2024 Annual Report on Form 10-K. We plan to adopt the interim reporting requirements in our Quarterly Report on Form 10-Q in the first quarter of 2025.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 2023, the FASB issued updated guidance on income tax disclosures. The new guidance requires companies to provide additional
    disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions and unrecognized deferred tax
    liabilities. This update is effective for annual periods beginning after December 15, 2024. Early adoption of this guidance is permitted. We currently plan to adopt this guidance in our 2025 Annual Report on Form 10-K.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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="c20230101to20231231"
      id="Text_f9a3c5dc257b427aabe07dd4809eeb67">
&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
    wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;).&lt;/div&gt;
</us-gaap:ConsolidationPolicyTextBlock>
    <us-gaap:UseOfEstimates
      contextRef="c20230101to20231231"
      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 United States, or
    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="c20230101to20231231"
      id="Text_774eb668f2cd4ae1bbca4e764a581e35">
&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 WAINUA 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 selling, general and administrative, or SG&amp;amp;A, expense and research and development, or 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: 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&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&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&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&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&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&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 may 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. When a partner exercises its option to license a
      medicine that was not previously determined to be a material right at the inception of the agreement 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.&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&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 that 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&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&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&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&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&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&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&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 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&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&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&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&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&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;"&gt;We recognize royalty revenue 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;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 Swedish Orphan Biovitrum AB, or 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; 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&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&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&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&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&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 Note 4, &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;
</us-gaap:RevenueFromContractWithCustomerPolicyTextBlock>
    <us-gaap:ReceivablesPolicyTextBlock
      contextRef="c20230101to20231231"
      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, 2023,
    approximately 87.8 percent of our contracts receivables were from one significant customer. As of December 31, 2022, approximately 82.5 percent of our contracts receivables were from one
    significant customer.&lt;/div&gt;
</us-gaap:ReceivablesPolicyTextBlock>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_OneSignificantCustomerMember"
      decimals="3"
      id="Fact_10e7a43398a0499b9e7ce86d84750009"
      unitRef="U003">0.878</us-gaap:ConcentrationRiskPercentage1>
    <ions:NumberOfSignificantCustomers
      contextRef="c20230101to20231231"
      decimals="INF"
      id="Fact_fa43dcb0b8ee41488642917fbbe8ac66"
      unitRef="U005">1</ions:NumberOfSignificantCustomers>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember"
      decimals="3"
      id="Fact_bb586f81c8674dd6b924c9686075aa5b"
      unitRef="U003">0.825</us-gaap:ConcentrationRiskPercentage1>
    <ions:NumberOfSignificantCustomers
      contextRef="c20220101to20221231"
      decimals="INF"
      id="Fact_3f1c8550953d4fb1bbaac07917b18557"
      unitRef="U005">1</ions:NumberOfSignificantCustomers>
    <us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy
      contextRef="c20230101to20231231"
      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="c20230101to20231231"
      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, 2023 and 2022, we recognized $78.2 million and $73.5 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="c20230101to20231231"
      decimals="-5"
      id="Fact_7a9ec3bea8ad464ca6e12c6aa16435cd"
      unitRef="U001">78200000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20220101to20221231"
      decimals="-5"
      id="Fact_ced6b030f6d146bb91eabbce81e6f413"
      unitRef="U001">73500000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:CostOfSalesPolicyTextBlock
      contextRef="c20230101to20231231"
      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="c20230101to20231231"
      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 R&amp;amp;D operations. We expense R&amp;amp;D costs as we incur them. When we make payments for R&amp;amp;D 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 R&amp;amp;D expenses are costs associated with our partner agreements. In 2023, 2022 and 2021, patent expenses were $4.3 million, $4.7 million and $5.3 million, respectively.&lt;/div&gt;
</us-gaap:ResearchAndDevelopmentExpensePolicy>
    <ions:PatentExpenses
      contextRef="c20230101to20231231"
      decimals="-5"
      id="Fact_85866a721e84472989175bb6188f4c57"
      unitRef="U001">4300000</ions:PatentExpenses>
    <ions:PatentExpenses
      contextRef="c20220101to20221231"
      decimals="-5"
      id="Fact_a0ff596166e44c50ba79c8d446d1bb4e"
      unitRef="U001">4700000</ions:PatentExpenses>
    <ions:PatentExpenses
      contextRef="c20210101to20211231"
      decimals="-5"
      id="Fact_18be9a3bed5e4b5a815b9ba827f8eb2d"
      unitRef="U001">5300000</ions:PatentExpenses>
    <us-gaap:IncomeTaxPolicyTextBlock
      contextRef="c20230101to20231231"
      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;
</us-gaap:IncomeTaxPolicyTextBlock>
    <us-gaap:EarningsPerSharePolicyTextBlock
      contextRef="c20230101to20231231"
      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 our net loss by our weighted-average number of common shares outstanding during the
    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;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, 2023,
    2022 and 2021, 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 from 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&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;&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&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;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&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&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&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&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&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&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 year ended December 31, 2023, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, 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;div style="display:none;"&gt;&lt;br/&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, 2023, 2022 and 2021, we had warrants related to our 0% Notes and 0.125% 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>
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      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
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      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
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      contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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      decimals="5"
      id="Fact_6f2d97c4eb3c416a953a12543f2d88d9"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
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      id="Fact_94aea085060d41bc80cec7916b6f1fdf"
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember"
      decimals="4"
      id="Fact_d78308e8178f4c7fb2b6e0190ad9d696"
      unitRef="U003">0.0175</us-gaap:DebtInstrumentInterestRateStatedPercentage>
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      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
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      decimals="5"
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      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_bd13f09db3d54fbbbdaf98adb97cd598"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_5607593758b2425c96658da021cfddf2"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy
      contextRef="c20230101to20231231"
      id="Text_ad082f24466d4b628f8d68f86e583d6f">
&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 years ended
    December 31, 2023 and 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; 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 we 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 PRSUs we granted in 2020 through 2022, &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. These PRSU awards also included an alternative three-year payout mechanism, or the Alternative Calculation, under
    which we must calculate an alternative payout at the end of the final three-year measurement period assuming the only measurement period for all
    shares under the award was the three-year period. If the Alternative Calculation is greater than payouts under the sum of the three years, then such PRSU award will pay out to achieve the number of shares payable under the Alternative Calculation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 PRSUs we granted in 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period
    based on our relative TSR as compared to a peer group of companies and as measured at the end of the 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 200 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 Note 8, &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;
</us-gaap:ShareBasedCompensationOptionAndIncentivePlansPolicy>
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      id="Fact_cef441d443044be391448d0eecd8a2b3"
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    <ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest
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    <us-gaap:ConcentrationRiskCreditRisk
      contextRef="c20230101to20231231"
      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="c20230101to20231231"
      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;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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;
</us-gaap:FairValueOfFinancialInstrumentsPolicy>
    <us-gaap:InvestmentPolicyTextBlock
      contextRef="c20230101to20231231"
      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 public and private biotechnology companies that we received as part
      of a technology license or partner agreement. At December 31, 2023, we held equity investments in three publicly traded companies and seven 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 publicly traded companies at their listed stock price. 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="c20231231"
      decimals="INF"
      id="Fact_b448547c88c7434cbc329f97a4b3ea28"
      unitRef="U007">3</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20231231"
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      id="Fact_5091e6339b9e4e85943dd42b9d332383"
      unitRef="U007">7</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <us-gaap:InventoryPolicyTextBlock
      contextRef="c20230101to20231231"
      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;
</us-gaap:InventoryPolicyTextBlock>
    <us-gaap:PropertyPlantAndEquipmentPolicyTextBlock
      contextRef="c20230101to20231231"
      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 we determine as the following (in years):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

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


  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt; &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Useful Lives&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;"&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 style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&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;/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;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>
    <ions:PropertyPlantAndEquipmentUsefulLivesTableTextBlock
      contextRef="c20230101to20231231"
      id="Text_ae9ad73d07bb4b9c96c8b308b9a0cddb">
&lt;div style="display:none;"&gt;&lt;br/&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 we determine as the following (in years):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

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


  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt; &lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; white-space: nowrap;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom;"&gt;&#160;&lt;/td&gt;

    &lt;td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Useful Lives&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;"&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 style="width: 19.66%; vertical-align: bottom; border-top: #000000 2px solid; background-color: #CCEEFF;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #FFFFFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;"&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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="width: 80.34%; vertical-align: bottom; background-color: #CCEEFF;"&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 style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;"&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;/tr&gt;


&lt;/table&gt;
</ions:PropertyPlantAndEquipmentUsefulLivesTableTextBlock>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember_RangeAxis_MinimumMember"
      id="Fact_b828ac0b40e9470bb076f1ca83c087f8">P3Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember_RangeAxis_MaximumMember"
      id="Fact_55512527b3f64093815e4719a3a9da7a">P10Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember_RangeAxis_MinimumMember"
      id="Fact_d29ce71868244871b343b50d2485de0e">P15Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember_RangeAxis_MaximumMember"
      id="Fact_dc8025be6cc74cca855f74c2367e8b3f">P40Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_LandImprovementsMember"
      id="Fact_ebc4b025a1eb42b69cfea73de031e5b1">P20Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember_RangeAxis_MinimumMember"
      id="Fact_a08cac9f5411485898c11087f1bef572">P5Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember_RangeAxis_MaximumMember"
      id="Fact_bda92ab03ee44df391ef93ce2060a192">P15Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember_RangeAxis_MinimumMember"
      id="Fact_8596a99804394834b242d29ed1c6c554">P5Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <us-gaap:PropertyPlantAndEquipmentUsefulLife
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember_RangeAxis_MaximumMember"
      id="Fact_2dd75df24eaa415ab54d1ac7e3d92e45">P10Y</us-gaap:PropertyPlantAndEquipmentUsefulLife>
    <ions:AccruedLiabilitiesPolicyPolicyTextBlock
      contextRef="c20230101to20231231"
      id="Text_c409370b54504175b0cd629ca3737408">
&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;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:AccruedLiabilitiesPolicyPolicyTextBlock>
    <us-gaap:DebtPolicyTextBlock
      contextRef="c20230101to20231231"
      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, 2023, we
    had three outstanding convertible senior notes, our 1.75% Notes, which mature in June 2028, our 0% Notes, which mature in April 2026, and
    our 0.125% Notes, which mature in December 2024. Refer to Note 7, &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="c20231231"
      decimals="INF"
      id="Fact_10f5114021fc4f5bb04196fe30354c8a"
      unitRef="U008">3</ions:DebtInstrumentNumberOfConvertibleNotes>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember"
      decimals="4"
      id="Fact_0da40ce130a0427ca4507455e50f00de"
      unitRef="U003">0.0175</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_88cf15606ae648ba879a91ce9224095e"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_637081ace1c3467395b29f412ee7c215"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DerivativesPolicyTextBlock
      contextRef="c20230101to20231231"
      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>
    <ions:LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock
      contextRef="c20230101to20231231"
      id="Text_d7ae37f96f1545d5a50ffc981607ee57">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Liability Related to Sale of Future 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;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 arrangements with Biogen and Novartis, respectively. Refer to Note 7, &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 the 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;Under our agreement with Royalty Pharma, we record upfront payments and milestone payments we receive from the sale of future royalties as
    a liability, net of transaction costs. We record royalty payments made to Royalty Pharma as a reduction of the liability or accrued interest and amortize the transaction costs over the estimated life of the royalty stream. We account for the associated
    interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the related product and recognizes the related 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 calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense using our
    current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material
    change in our estimate, we will prospectively adjust the effective interest rate and the related interest expense.&lt;/div&gt;
</ions:LiabilityRelatedToSaleOfFutureRoyaltiesPolicyPolicyTextBlock>
    <us-gaap:LesseeLeasesPolicyTextBlock
      contextRef="c20230101to20231231"
      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="c20230101to20231231"
      id="Text_1f633c4a698f418f8aaba786d26a86aa">
&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;We operate 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.&lt;/div&gt;
</us-gaap:SegmentReportingPolicyPolicyTextBlock>
    <us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock
      contextRef="c20230101to20231231"
      id="Text_702601a4d67748f5a98dd7344990b6c7">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Recently Issued 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 November 2023, the Financial Accounting Standards Board, or FASB, issued updated guidance on segment reporting. The guidance requires
    public companies with a single reportable segment to provide all disclosures required under ASC 280, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Segment Reporting&lt;/span&gt;. In addition, the guidance
    requires public companies to include in interim reports all disclosures related to a reportable segment's profit or loss and assets that are currently required in annual reports. This update is effective for annual periods beginning after December 15,
    2023 and interim periods beginning after December 15, 2024. The guidance is applied on a retrospective basis for all periods presented in the financial statements, unless it is impracticable. Early adoption of this guidance is permitted. We currently
    plan to adopt the annual reporting requirements in our 2024 Annual Report on Form 10-K. We plan to adopt the interim reporting requirements in our Quarterly Report on Form 10-Q in the first quarter of 2025.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 2023, the FASB issued updated guidance on income tax disclosures. The new guidance requires companies to provide additional
    disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions and unrecognized deferred tax
    liabilities. This update is effective for annual periods beginning after December 15, 2024. Early adoption of this guidance is permitted. We currently plan to adopt this guidance in our 2025 Annual Report on Form 10-K.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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:SupplementalBalanceSheetDisclosuresTextBlock
      contextRef="c20230101to20231231"
      id="Text_49076dbe5ad448cdb9a7bcb57a3d6075">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2. Supplemental Financial Data&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;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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/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;20,985&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;17,061&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;/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;1,809&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;2,699&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;/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;22,794&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;5,477&lt;/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;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;/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;154&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;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;/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;28,425&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;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;/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;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;Our property, plant and equipment 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="background-color: #CCEEFF; vertical-align: bottom; white-space: nowrap; width: 76%;"&gt;
          &lt;div style="text-align: left; margin-left: 6.6pt; 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; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;79,885&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;74,351&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -2.4pt; 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; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,228&lt;/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;41,158&lt;/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: -2.4pt; 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; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,276&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;28,357&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -2.4pt; 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; 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;9,844&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;9,575&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;&#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;159,233&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" 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%; 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: -2.4pt; 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;" valign="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;(96,759&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;(87,716&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;&#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;62,474&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;65,725&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -2.4pt; 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;" valign="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;8,569&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;8,569&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; margin-left: 33.6pt; 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; 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;71,043&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;74,294&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: 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/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;105,967&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;7,454&lt;/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;7,945&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;/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;4,875&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;29,598&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;12,198&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;/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;147,894&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;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;/tr&gt;


&lt;/table&gt;
</us-gaap:SupplementalBalanceSheetDisclosuresTextBlock>
    <us-gaap:ScheduleOfInventoryCurrentTableTextBlock
      contextRef="c20230101to20231231"
      id="Text_a9f4657750f748f0873e72b36f2a3b63">
&lt;div style="display:none;"&gt;&lt;br/&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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/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;20,985&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;17,061&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;/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;1,809&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;2,699&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;/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;22,794&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;5,477&lt;/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;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;/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;154&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;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;/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;28,425&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;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;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfInventoryCurrentTableTextBlock>
    <us-gaap:InventoryRawMaterials
      contextRef="c20231231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_6bd04232b4f2486792569ed8d521fec8"
      unitRef="U001">20985000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20221231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_6f814b2671fc4497a5ac6e3ef30f9e41"
      unitRef="U001">17061000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20231231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_8c7edca83ce54077abaf796386024e7f"
      unitRef="U001">1809000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20221231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_220e17cc8d2648de9bb56af981e1f8a8"
      unitRef="U001">2699000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20231231"
      decimals="-3"
      id="Fact_1f8903f0de9f465ebbccd820af3fe141"
      unitRef="U001">22794000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20221231"
      decimals="-3"
      id="Fact_8ea29e125e384a0b85cbcc7cd0bf8de8"
      unitRef="U001">19760000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20231231"
      decimals="-3"
      id="Fact_666c46286abc442fbebc6baa888f870c"
      unitRef="U001">5477000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20221231"
      decimals="-3"
      id="Fact_b6b68af9767b48ce9e4195a93e54aa64"
      unitRef="U001">2109000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20231231"
      decimals="-3"
      id="Fact_2ce24e72453c4c46aabcad3d73fe6284"
      unitRef="U001">154000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20221231"
      decimals="-3"
      id="Fact_24167fa6e6d442398490541d6ad73f36"
      unitRef="U001">164000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryNet
      contextRef="c20231231"
      decimals="-3"
      id="Fact_4803a14d03d74237b17f8d63e8173b4c"
      unitRef="U001">28425000</us-gaap:InventoryNet>
    <us-gaap:InventoryNet
      contextRef="c20221231"
      decimals="-3"
      id="Fact_346da7c3659d43908f2c18156ff2131f"
      unitRef="U001">22033000</us-gaap:InventoryNet>
    <us-gaap:PropertyPlantAndEquipmentTextBlock
      contextRef="c20230101to20231231"
      id="Text_2add9cef486d4c08a940716c68c05cb1">
&lt;div style="display:none;"&gt;&lt;br/&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 property, plant and equipment 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="background-color: #CCEEFF; vertical-align: bottom; white-space: nowrap; width: 76%;"&gt;
          &lt;div style="text-align: left; margin-left: 6.6pt; 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; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;79,885&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;74,351&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -2.4pt; 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; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,228&lt;/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;41,158&lt;/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: -2.4pt; 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; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,276&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;28,357&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -2.4pt; 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; 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;9,844&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;9,575&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;&#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;159,233&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" 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%; 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: -2.4pt; 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;" valign="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;(96,759&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;(87,716&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;&#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;62,474&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;65,725&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -2.4pt; 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;" valign="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;8,569&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;8,569&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; margin-left: 33.6pt; 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; 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;71,043&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;74,294&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:PropertyPlantAndEquipmentTextBlock>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember"
      decimals="-3"
      id="Fact_3f415076adb64aefb62a6200aa09373b"
      unitRef="U001">79885000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_EquipmentAndComputerSoftwareMember"
      decimals="-3"
      id="Fact_853375bcf45b4e2292895881e2f2165f"
      unitRef="U001">74351000</us-gaap:PropertyPlantAndEquipmentGross>
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      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember"
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      id="Fact_be347fecf99442269a1147ce15f0acde"
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    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_BuildingAndBuildingImprovementsMember"
      decimals="-3"
      id="Fact_55e9ea1cd6d04777a5fd335b1d632465"
      unitRef="U001">41158000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
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      decimals="-3"
      id="Fact_8771d2aee3184880a9f8683acca837e9"
      unitRef="U001">28276000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember"
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      id="Fact_afa97b7033ec449abdf9f88c730430b3"
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      unitRef="U001">9844000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_FurnitureAndFixturesMember"
      decimals="-3"
      id="Fact_91cf4808a4ff4d89b617433a31ee3716"
      unitRef="U001">9575000</us-gaap:PropertyPlantAndEquipmentGross>
    <us-gaap:PropertyPlantAndEquipmentGross
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember"
      decimals="-3"
      id="Fact_7f69b083e88341d0a10c7007be88479a"
      unitRef="U001">159233000</us-gaap:PropertyPlantAndEquipmentGross>
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      contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember"
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      contextRef="c20221231"
      decimals="-3"
      id="Fact_be9d2cd137b9488d8e04e6515601bea3"
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    <us-gaap:PropertyPlantAndEquipmentNet
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_PropertyPlantAndEquipmentExcludingLandMember"
      decimals="-3"
      id="Fact_4007d53a89214452be36c3718789c2f6"
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      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_LandMember"
      decimals="-3"
      id="Fact_c9348a3d1fce44199a8e4bed4478b232"
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      contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_LandMember"
      decimals="-3"
      id="Fact_d9ffdb0b4d834bedb849aa2a434edef4"
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      contextRef="c20221231"
      decimals="-3"
      id="Fact_90431cc0470047e4b4d48b3cd20bde96"
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    <us-gaap:ScheduleOfAccruedLiabilitiesTableTextBlock
      contextRef="c20230101to20231231"
      id="Text_2045eb16e89646bfa0fb76a5f5050910">
&lt;div style="display:none;"&gt;&lt;br/&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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/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;105,967&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;7,454&lt;/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;7,945&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;/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;4,875&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;29,598&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;12,198&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;/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;147,894&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;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;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfAccruedLiabilitiesTableTextBlock>
    <ions:AccruedClinicalDevelopmentExpenses
      contextRef="c20231231"
      decimals="-3"
      id="Fact_a67b9aa3ded9444ea6fa8750f375469c"
      unitRef="U001">105967000</ions:AccruedClinicalDevelopmentExpenses>
    <ions:AccruedClinicalDevelopmentExpenses
      contextRef="c20221231"
      decimals="-3"
      id="Fact_6080a8023b8a4a7680a671237d572043"
      unitRef="U001">116460000</ions:AccruedClinicalDevelopmentExpenses>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_97e185cf18574068bda549c444019ebd"
      unitRef="U001">7454000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20221231"
      decimals="-3"
      id="Fact_99a4ffc78cea4ea79a97e34f63ad0e36"
      unitRef="U001">7945000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_a85290633cb748aa801b0128951ad078"
      unitRef="U001">4875000</ions:AccruedCommercialExpensesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20221231"
      decimals="-3"
      id="Fact_6e4c39c15d234eb09c433b9792328307"
      unitRef="U001">3498000</ions:AccruedCommercialExpensesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_159ba94a17f648459aba5b5549ce591d"
      unitRef="U001">29598000</us-gaap:OtherAccruedLiabilitiesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20221231"
      decimals="-3"
      id="Fact_ec657cc584984d58a779e475cb9c827b"
      unitRef="U001">12198000</us-gaap:OtherAccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_c527b3021abd4093a2c21fd084cef7d4"
      unitRef="U001">147894000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20221231"
      decimals="-3"
      id="Fact_8efb348efdaa4293a28fe2308d0572ac"
      unitRef="U001">140101000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:RevenueFromContractWithCustomerTextBlock
      contextRef="c20230101to20231231"
      id="Text_8fa4a07991ac4286b221053dfdaeed02">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;3. Revenues&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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;During the years ended December 31, &lt;/span&gt;2023&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, our revenues were comprised 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;&#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="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; &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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&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;" 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;Commercial revenue:&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: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;240,379&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;242,314&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;267,776&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other commercial 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;&#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: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;TEGSEDI and WAYLIVRA revenue, net&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,913&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;30,051&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;55,500&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty 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;33,299&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;30,993&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;19,119&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: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total other commercial revenue&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;68,212&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;61,044&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;74,619&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: left; text-indent: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial 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;308,591&lt;/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;303,358&lt;/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;342,395&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;&#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;Research and development 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;&#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: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Collaborative agreement 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;352,657&lt;/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;207,222&lt;/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;468,061&lt;/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: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;WAINUA joint development revenue&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;126,399&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;76,787&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: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total research and development 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;479,056&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;284,009&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;468,061&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: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue&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;787,647&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;587,367&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;810,456&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="display:none;"&gt;&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; 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;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. We earn royalty revenue on net sales of
    QALSODY which is included in 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: 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We earn commercial revenue from TEGSEDI and WAYLIVRA sales
      under our distribution agreements with &lt;/span&gt;Sobi&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. In addition, we receive royalties from&lt;/span&gt; PTC Therapeutics International Limited, or PTC, for TEGSEDI&#160; and WAYLIVRA
    sales. Refer to Note 4, &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 details on our commercialization partnerships with Sobi and PTC.&lt;/div&gt;

&lt;div&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;&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 variable 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 payment 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 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 who 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;WAINUA (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 WAINUA
    for the treatment of transthyretin amyloidosis, or ATTR. We jointly developed and are preparing to commercialize WAINUA with AstraZeneca in the U.S. We initially granted AstraZeneca exclusive rights to commercialize WAINUA outside the U.S., except for
    certain Latin American countries. In July 2023, we expanded those rights to include 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 WAINUA 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 WAINUA 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:RevenueFromContractWithCustomerTextBlock>
    <us-gaap:DisaggregationOfRevenueTableTextBlock
      contextRef="c20230101to20231231"
      id="Text_9914efd2504d4b07a8cc31caeee2e3b1">
&lt;div style="display:none;"&gt;&lt;br/&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;During the years ended December 31, &lt;/span&gt;2023&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, our revenues were comprised 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;&#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="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; &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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue:&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;" 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;Commercial revenue:&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: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;240,379&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;242,314&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;267,776&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other commercial 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;&#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: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;TEGSEDI and WAYLIVRA revenue, net&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,913&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;30,051&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;55,500&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Licensing and other royalty 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;33,299&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;30,993&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;19,119&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: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total other commercial revenue&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;68,212&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;61,044&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;74,619&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: left; text-indent: 18pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total commercial 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;308,591&lt;/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;303,358&lt;/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;342,395&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;&#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;Research and development 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;&#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: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Collaborative agreement 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;352,657&lt;/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;207,222&lt;/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;468,061&lt;/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: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;WAINUA joint development revenue&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;126,399&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;76,787&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: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 36pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total research and development 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;479,056&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;284,009&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;468,061&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: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue&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;787,647&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;587,367&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;810,456&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="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;4. 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. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. Under our 2013 strategic neurology collaboration, Biogen developed QALSODY (tofersen), our medicine that received
    accelerated approval in the U.S. to treat patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS. In addition, we and Biogen are currently developing numerous other investigational medicines to treat neurodegenerative diseases,
    including medicines in development to treat people with amyotrophic lateral sclerosis, or ALS, SMA, Angelman Syndrome, or AS, Alzheimer&#x2019;s disease, or AD, and Parkinson&#x2019;s disease, or PD. 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, 2023, we
    have received nearly $3.8 billion from our Biogen collaborations, including payments to purchase our 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: 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 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, 2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we earned more than $&lt;/span&gt;2.1&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;1.6&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 2023, we entered into a royalty purchase agreement with Royalty Pharma in which Royalty Pharma receives 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 the U.S. Food and Drug Administration, or FDA, approval of pelacarsen, which Novartis is developing.
    Refer to Note 7, &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 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;.&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;At the commencement of this
      collaboration, 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 from Biogen. In &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2021&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, Biogen
      exercised its option to license ION&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;306&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, a drug we
      discovered under this collaboration, for which &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;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. We recognized this payment as revenue in full because&lt;/span&gt; Biogen had full use of the license without any continuing involvement from us. 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;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 ION&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;306&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, 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 $555 million if Biogen advances ION306, which is comprised of 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 from any product that Biogen successfully commercializes under this collaboration.&lt;/span&gt; From inception through December 31, 2023, 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; 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 2018, we and Biogen entered into a strategic collaboration
      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 &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 targets&lt;/span&gt;. In most cases, Biogen will be 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 has 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;At the commencement of this collaboration, &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;For each medicine under this 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. &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 from any product that Biogen successfully commercializes under this collaboration.&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. From inception through December 31, 2023, we have received nearly $1.1 billion in payments under this collaboration, including payments to purchase our stock. We will achieve the next payment of up to $15 million if Biogen licenses a medicine&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;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, 2023,
    we have included $623 million &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;in upfront and milestone payments in
      the transaction price for our R&amp;amp;D services performance obligation under this collaboration, including a $&lt;/span&gt;7.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone payment we achieved in the fourth quarter of 2023. This milestone payment did not create a new performance obligation because it is part of our original R&amp;amp;D services
      performance obligation. Therefore, we included this amount 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 2013, we and Biogen entered into a 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. In
    most cases, we are 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 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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 currently advancing four
    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 (QALSODY and ION541) and &lt;span style="-sec-ix-hidden:Fact_7b05dc571fcb46f8bbbe0db51a44d460"&gt;a&lt;/span&gt;
    medicine for multiple system atrophy (ION464). In 2018, Biogen exercised its option to license QALSODY, our medicine that received accelerated approval in April 2023 from the FDA for the treatment of adult patients with SOD1-ALS. As a result, Biogen is
    responsible for global development, regulatory and commercialization activities and costs for QALSODY.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 QALSODY, we are eligible to receive nearly $110 million, which is comprised of a $35 million license fee we received when Biogen
    licensed QALSODY from us in 2018, $18 million in development milestone payments and up to $55 million in regulatory milestone payments. In addition, we are eligible to receive tiered royalties ranging from 11 percent to 15 percent on net sales of QALSODY. We will achieve the next milestone
    payment for QALSODY of $20 million if the European Medicines Agency, or EMA, approves Biogen&#x2019;s Marketing Authorization Application, or MAA,
    filing of QALSODY.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 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 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, 2023, we have received more than $325 million in payments under our 2013 strategic neurology collaboration. We will achieve the next payment of $70 million if Biogen licenses 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 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; R&amp;amp;D 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 period we generated the payment because we did not have any performance obligations for the
      respective payment. For example, in 2023, we earned a &lt;/span&gt;$16&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;million








      milestone payment from Biogen when the FDA approved Biogen&#x2019;s New Drug Application, or NDA, for QALSODY, which we recognized in full because we did not have any remaining 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 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. In 2019, Biogen exercised its option to license IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; and as a result 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;&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. For each program under this
      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 license fee of up to $&lt;/span&gt;70&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;
      million, 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 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, 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, 2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we have received more than $&lt;/span&gt;230&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in payments under this collaboration, including $&lt;/span&gt;39&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
      during 2023 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 $&lt;/span&gt;70&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;million if Biogen licenses ION582 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;When we commenced development for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; and ION582, we identified two separate performance obligations as our development work for each medicine. 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 obligations. In 2022, we completed our R&amp;amp;D services performance obligation for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;. From inception through December 31, 2023, 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;. From inception through December 31, 2023, we have included $68 million in milestone payments in the transaction price for our ION582 development performance obligation, including $39 million in milestone payments we received from Biogen for advancing ION582 during 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;During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in thousands, 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;350,146&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;366,696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;428,784&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: 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;44&lt;/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;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;/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;2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred
      revenue of $&lt;/span&gt;307.4&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;351.2&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;WAINUA (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 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for
    the treatment of ATTR. In December 2023, the FDA approved eplontersen with the brand name, WAINUA, in the U.S. for ATTRv-PN. We are jointly developing and commercializing WAINUA with AstraZeneca in the U.S. We initially granted AstraZeneca exclusive
    rights to commercialize WAINUA outside the U.S., except for certain Latin American countries. In July 2023, we expanded those rights to include 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;&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 up to $&lt;/span&gt;3.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion, which is comprised of a $&lt;/span&gt;200&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment, a $&lt;/span&gt;20&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million license fee, up to $&lt;/span&gt;485&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in development and approval milestone payments and up to $&lt;/span&gt;2.9&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion in sales milestone payments. The agreement includes territory-specific development,
      commercial and medical affairs cost-sharing provisions. In addition, we are eligible to receive up to mid-&lt;/span&gt;20 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; royalties for sales in the U.S. and tiered royalties ranging from mid to high teens for sales outside the U.S. From inception through &lt;/span&gt;December 31, 2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we have received nearly $&lt;/span&gt;360&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in payments under this collaboration. We will achieve the next payment of $&lt;/span&gt;30&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upon regulatory approval of WAINUA for ATTRv-PN in the EU 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;We evaluated our WAINUA 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 in 2021. In 2023, we earned a $20 million license fee payment when we licensed rights to Latin America for WAINUA to AstraZeneca. We recognized these payments in full because we did not have any remaining performance
    obligations after we delivered the licenses 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 WAINUA 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. In 2023, we earned a $50 million milestone payment when the FDA approved WAINUA for ATTRv-PN in the
    U.S. We recognized this milestone payment in full as joint development revenue because we did not have any remaining performance obligations related to the milestone payment.&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 WAINUA, we have a collaboration with AstraZeneca focused on discovering and developing treatments for
    cardiovascular, renal and metabolic diseases, which we formed in 2015. 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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 $3.4 billion, which is comprised of a $65 million upfront payment, up to $290 million in license fees, up to $865 million
    in development milestone payments and up to $2.2 billion in regulatory 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, 2023, we have received more than $300 million in payments under this
    collaboration. We will achieve the next payment of $10 million 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;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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; 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 period we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. For example, in 2023, we earned a
    $36 million payment when AstraZeneca licensed ION826 from us. We recognized this payment in full in 2023 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;During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with AstraZeneca (in thousands, 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;Revenue from our relationship with AstraZeneca&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;202,236&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;79,160&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;254,591&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;26&lt;/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;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;/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, 2023 and 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-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 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. Upon initiating the collaboration, we received an upfront payment of $35
    million. Under our collaboration, GSK is developing bepirovirsen for the treatment of chronic hepatitis B virus infection, or 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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 and commercializes
    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, 2023, we have received more than $105 million in an upfront payment and payments related to 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;We completed our R&amp;amp;D services performance obligations in 2015, therefore 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 2023, we earned a $&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone payment when GSK initiated a Phase 3 program of
      bepirovirsen. We recognized this milestone payment as R&amp;amp;D revenue in full in 2023 because we did not have any remaining performance obligations related to the milestone payment. 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, 2023, 2022 and 2021, we earned the following revenue from our relationship with GSK (in thousands, 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;Revenue from our relationship with GSK&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;15,000&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;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;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&lt;/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: 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, 2023 and 2022.&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;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; font-style: italic;"&gt;Pelacarsen 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;In 2017, we initiated a collaboration with Novartis to
      develop and commercialize pelacarsen.&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 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;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. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through &lt;/span&gt;December 31, 2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we have received more than $&lt;/span&gt;275&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in payments under this collaboration. 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 $&lt;/span&gt;50&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million if the FDA accepts an NDA filing 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 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&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&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&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&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&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&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 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&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&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&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&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&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;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 Note 7, &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 Medicine for the Treatment of Lp(a)-Driven Cardiovascular 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 August 2023, we entered into a collaboration and license agreement with Novartis for the discovery, development and commercialization
    of a novel medicine for patients with Lp(a)-driven cardiovascular disease, or CVD. Novartis is solely responsible for the development, manufacturing and potential commercialization of the next generation Lp(a) therapy.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 $730 million, which is comprised of a $60 million upfront payment, up to $155 million in development milestone payments, up to $105
    million in regulatory milestone payments and up to $410 million in sales milestone payments. In addition, we are eligible to receive tiered
    royalties ranging from 10 percent to 20 percent
    on net sales. From inception through December 31, 2023, we have received $60 million from the upfront payment we received under this collaboration. We will achieve the next payment of $5 million if we designate a development candidate 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 Novartis. We determined the transaction price to be the $60 million upfront payment we received in the fourth quarter 2023. We allocated the transaction price 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. We currently estimate we will satisfy our performance obligation at the
    end of the research term in June 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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Novartis (in thousands, 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;Revenue from our relationship with Novartis&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;30,194&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;237&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;25,526&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;&#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;Percentage of total revenue&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;4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less than 1%&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;3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" 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 consolidated balance sheet at December 31, 2023 included deferred revenue of $30.0 million related to our relationship with Novartis. We did not have any deferred revenue from our relationship with Novartis at 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-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 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 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. As a result, 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 collaboration. From inception through December 31, 2023, 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 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 period in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In 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 independent data monitoring committee, or 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 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 multiple 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 immunoglobulin A, or IgA, nephropathy, or IgAN, and one for the treatment of patients with GA, the advanced stage of dry AMD. In April 2023, Roche initiated a Phase 3 study of IONIS-FB-L&lt;sub&gt;Rx&lt;/sub&gt; in patients with IgAN.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 in patients
      with IgAN, &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;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 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 milestone payments, up to $&lt;/span&gt;279&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in regulatory milestone payments 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, 2023,
    we have received more than $135 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. From inception through December 31, 2023, we have included $97 million in upfront and milestone payments in
    the transaction price for our R&amp;amp;D services performance obligation under this collaboration, including $22 million of milestone payments we
    achieved in 2022. 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 fourth 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; font-style: italic;"&gt;RNA-Targeting Medicines for Alzheimer's Disease and Huntington'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 September 2023, we entered into an agreement with Roche to develop two undisclosed early-stage programs for RNA-targeting investigational medicines for the treatment of AD and HD. Under the agreement, we are responsible for advancing the two programs through preclinical studies and Roche is responsible for clinical development, manufacturing and commercialization of the medicines if they
    receive regulatory approval.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 $625 million, which is comprised of a $60 million upfront payment, up to $167 million in development milestone payments and up to $398
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales. From inception through December 31, 2023, we have received $60 million from the upfront payment we received under this collaboration. We will achieve the next
    payment of $7.5 million if we advance 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;We identified two performance
    obligations under this new agreement, comprised of R&amp;amp;D services for each of the two separate programs. We determined the transaction price
    to be the $60 million upfront payment we received in the fourth quarter 2023. 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&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;$45 million for the R&amp;amp;D services for the investigational
            medicine for AD; 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&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;15&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million for the R&amp;amp;D services for t&lt;/span&gt;he investigational medicine for HD.&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 are recognizing revenue for our R&amp;amp;D services performance obligations as we perform services based on our effort to satisfy our
    performance obligations relative to our total effort expected to satisfy our performance obligations. We currently estimate we will satisfy our performance obligations at the end of the research terms of March 2024 and March 2025 for the
    investigational medicines for AD and HD, 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;During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with Roche (in thousands, 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;Revenue from our relationship with Roche&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;48,838&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;67,202&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;17,241&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;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;/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;2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred
      revenue of $&lt;/span&gt;36.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;22.4&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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Otsuka&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 2023, we entered into an agreement with Otsuka Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe.
    We are responsible for the ongoing development of donidalorsen. We retained the rights to commercialize donidalorsen in the U.S. and in the rest of the world assuming regulatory approval.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 $185 million, which is comprised of a $65 million upfront payment, up to $50 million in regulatory milestone payments and up to $70
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties ranging from 20 percent to 30 percent on net sales. From inception through December 31, 2023, we have received $65 million from the upfront payment we received under this collaboration. We will achieve the next
    payment of $15 million if the EMA accepts a MAA filing for donidalorsen in the EU 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;We identified two performance
    obligations under this new agreement, comprised of our license of donidalorsen to Otsuka and R&amp;amp;D services for donidalorsen. We determined the transaction price to be the $65 million upfront payment we received in the fourth quarter 2023. 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&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;$56 million for the license of donidalorsen; 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&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;$9 million for the R&amp;amp;D services for donidalorsen.&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 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 obligations in March 2026.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 year ended December 31, 2023, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amount):&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;" 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: 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; 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;/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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Otsuka&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;56,480&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -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;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;&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;2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred revenue of $&lt;/span&gt;8.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;
      million related to our relationship with Otsuka.&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-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 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 and September 2023, we started receiving
    royalties from PTC for TEGSEDI and WAYLIVRA sales, respectively&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-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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In 2021, we began commercializing TEGSEDI and WAYLIVRA in
      Europe and TEGSEDI in North America through distribution agreements with Sobi. &lt;/span&gt;Under our distribution agreements, Sobi is responsible for commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. We are
    responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. Under our agreements with Sobi, Sobi does not generally have a right of return. We recognize as revenue the price Sobi
    pays us for the inventory when we deliver the finished goods inventory to Sobi. In addition, 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;In October 2023, our distribution agreement for TEGSEDI in North America was terminated. As a result, we are currently transitioning
    responsibilities from Sobi to us in order to continue serving the impacted patient community. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In February 2024, we began the process to withdraw the TEGSEDI NDA.&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, 2023, 2022 and 2021, we earned the following revenue from our distribution agreement with Sobi for TEGSEDI in North America (in thousands, 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;TEGSEDI revenue from our distribution agreement with Sobi in North America&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;2,646&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;4,004&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;7,443&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less than 1%&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;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&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;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" 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="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 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 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 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.&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&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 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 and will pay Metagenomi certain fees for the selection of genetic targets. 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. In addition, we will pay
    Metagenomi milestone payments and royalties that are contingent on the achievement of certain development, regulatory and sales events. We will also 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 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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Alnylam (in thousands, 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;Revenue from our relationship with Alnylam&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;
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    &lt;td colspan="1" style="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;$&lt;/div&gt;
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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,389&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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="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;
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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;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;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;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;/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
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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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in thousands, 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;350,146&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;366,696&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;428,784&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: 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;44&lt;/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;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;/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, 2023, 2022 and 2021, we earned the following revenue from our relationship with AstraZeneca (in thousands, 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;Revenue from our relationship with AstraZeneca&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;202,236&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;79,160&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;254,591&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;26&lt;/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;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;/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, 2023, 2022 and 2021, we earned the following revenue from our relationship with GSK (in thousands, 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;

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    &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;

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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2023&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;2022&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;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: 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;Revenue from our relationship with GSK&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;15,000&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;

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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;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&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;During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with Novartis (in thousands, 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;

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    &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;
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    &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;2023&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;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;

    &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;/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;Revenue from our relationship with Novartis&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;30,194&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;237&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,526&lt;/div&gt;
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          &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="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;4&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;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less than 1%&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="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;3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; 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="display:none;"&gt;&lt;br/&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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Roche (in thousands, 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;

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  &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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;Revenue from our relationship with Roche&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;48,838&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;67,202&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;17,241&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;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;/tr&gt;


&lt;/table&gt;
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    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
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      unitRef="U001">67202000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
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      unitRef="U003">0.06</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember"
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      id="Fact_cf5ca05dc07c4448bdda2353f8ed8769"
      unitRef="U003">0.11</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember"
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      id="Fact_6490dfcad60e494083f50ae6646f73e4"
      unitRef="U003">0.02</us-gaap:ConcentrationRiskPercentage1>
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      decimals="-5"
      id="Fact_5ff4d7b8efd14d4a81981ea0cfa0cf58"
      unitRef="U001">36700000</us-gaap:ContractWithCustomerLiability>
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      contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationsMember"
      decimals="-5"
      id="Fact_a38902f403274142aedd7c7ed42e8214"
      unitRef="U001">22400000</us-gaap:ContractWithCustomerLiability>
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      contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="-6"
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      contextRef="c20231001to20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
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      id="Fact_8a8d9e182b6846d8aa9b4ac6ec87b7b0"
      unitRef="U001">65000000</ions:UpfrontPaymentReceived>
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      contextRef="c20230101to20231231_RangeAxis_MinimumMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="2"
      id="Fact_d53ff3dfc7e5444fb6b236e2bece9a73"
      unitRef="U003">0.20</ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine>
    <ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine
      contextRef="c20230101to20231231_RangeAxis_MaximumMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="2"
      id="Fact_d5b20d1cba704a8cb0fffbe29fba3f2b"
      unitRef="U003">0.30</ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine>
    <ions:CumulativePaymentsReceived
      contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="-6"
      id="Fact_8bacb479b10f4a519b6f9f0b60fdf84f"
      unitRef="U001">65000000</ions:CumulativePaymentsReceived>
    <ions:NextPaymentToBeAchieved
      contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="-6"
      id="Fact_c1d2152e2c604418a9c3c7376ad14171"
      unitRef="U001">15000000</ions:NextPaymentToBeAchieved>
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      contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="INF"
      id="Fact_27fb7f4e535a470eaab5dc07fee5038a"
      unitRef="U011">2</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
    <ions:RevenueFromContractWithCustomerTransactionPrice
      contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="-6"
      id="Fact_ebadc349803b440ebdc2ca77c18844a0"
      unitRef="U001">65000000</ions:RevenueFromContractWithCustomerTransactionPrice>
    <ions:RevenueFromContractWithCustomerTransactionPrice
      contextRef="c20231231_ProductOrServiceAxis_LicenseOfDonidalorsenMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="-6"
      id="Fact_bc5e5327115f4deea2ae75dc63832c93"
      unitRef="U001">56000000</ions:RevenueFromContractWithCustomerTransactionPrice>
    <ions:RevenueFromContractWithCustomerTransactionPrice
      contextRef="c20231231_ProductOrServiceAxis_ResearchAndDevelopmentServicesForDonidalorsenMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="-6"
      id="Fact_78ea72b1d4a54c649943487acf03c123"
      unitRef="U001">9000000</ions:RevenueFromContractWithCustomerTransactionPrice>
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      contextRef="c20230101to20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
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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 year ended December 31, 2023, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amount):&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;" 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: 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; 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;/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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue from our relationship with Otsuka&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;56,480&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -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;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="c20230101to20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="-3"
      id="Fact_98b462a9e7fd40f9b553badad1b1fc26"
      unitRef="U001">56480000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20230101to20231231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="2"
      id="Fact_549b2d646eb14c15854f24d79f008c74"
      unitRef="U003">0.07</us-gaap:ConcentrationRiskPercentage1>
    <us-gaap:ContractWithCustomerLiability
      contextRef="c20231231_TypeOfArrangementAxis_OtsukaPharmaceuticalCoLtdCollaborationMember"
      decimals="-5"
      id="Fact_ab2db9a4c2814c19ba0f374053b31f7e"
      unitRef="U001">8500000</us-gaap:ContractWithCustomerLiability>
    <ions:RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner
      contextRef="c20230101to20231231_TypeOfArrangementAxis_PtcTherapeuticsCollaborationMember"
      decimals="2"
      id="Fact_570d071a48d248dbb4cd460b720cd572"
      unitRef="U003">0.20</ions:RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner>
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      contextRef="c20230101to20231231_TypeOfArrangementAxis_SwedishOrphanBiovitrumABDistributionAgreementMember"
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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, 2023, 2022 and 2021, we earned the following revenue from our distribution agreement with Sobi for TEGSEDI in North America (in thousands, 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;TEGSEDI revenue from our distribution agreement with Sobi in North America&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;2,646&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;4,004&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;7,443&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less than 1%&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;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&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;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" 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, 2023, 2022 and 2021, we earned the following revenue from our relationship with Alnylam (in thousands, 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;Revenue from our relationship with Alnylam&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;28,426&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;21,389&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;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;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;/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;5. 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, 2023:&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;68&lt;/div&gt;
        &lt;/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;24&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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;" 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: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);" 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%; background-color: rgb(255, 255, 255); border-bottom: 4px double rgb(0, 0, 0); white-space: nowrap;" 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, 2023,
    92 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;We invest in debt securities with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard &amp;amp;
    Poor&#x2019;s, Moody&#x2019;s or Fitch, 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;At December 31, 2023, we had an ownership interest of less than 20 percent &lt;/span&gt;in seven
    private companies and three public 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 style="display:none;"&gt;&lt;br/&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, 2023&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;559,967&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;157&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(2,625&lt;/div&gt;
        &lt;/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;557,499&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;224,711&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;64&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;(611&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;224,164&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;513,784&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;152&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(1,889&lt;/div&gt;
        &lt;/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;512,047&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;17,757&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;42&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;(113&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;17,686&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; margin-left: 18pt; 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;1,316,219&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;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;415&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;(5,238&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;1,311,396&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;243,151&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;1,270&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;(692&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;243,729&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;110,138&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;547&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(21&lt;/div&gt;
        &lt;/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;110,664&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;294,873&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;1,239&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;(480&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;295,632&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;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: #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;3,466&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&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;(4&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;3,469&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; margin-left: 18pt; 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: #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;651,628&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;3,063&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;(1,197&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;653,494&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: 27pt; 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: #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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,967,847&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,478&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,435&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,964,890&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;Equity 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;&#160;&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;&#160;&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;&#160;&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;&#160;&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;Publicly traded 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: #CCEEFF;" valign="bottom"&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;11,897&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;236&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(5,832&lt;/div&gt;
        &lt;/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;6,301&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;Privately held 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: #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;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: #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;25,001&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;(5,125&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;42,991&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; margin-left: 18pt; 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: #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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" 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: #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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,237&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,957&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49,292&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; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36pt; 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: #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;
          &lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,002,859&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;&#160;&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,715&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;&#160;&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(17,392&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;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;
          &lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,014,182&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;&#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, 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; margin-left: 18pt; 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; margin-left: 18pt; 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; margin-left: 36pt; 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; 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;Publicly traded 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;Privately held 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; margin-left: 18pt; 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; margin-left: 36pt; 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 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 publicly traded equity securities are included in other current
            assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2023, we recorded a $4.2 million net &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;unrealized loss in our consolidated statements of
              operations related to changes in the fair value of our investments in publicly traded companies.&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;(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 privately held equity securities are included in deposits and other assets. We recognize our privately held 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, which are Level 3 inputs. In the year ended December 31, 2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we recorded a $&lt;/span&gt;2.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million net unrealized gain in our consolidated statements of operations related to changes in the fair value of our investments in privately held companies.&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, 2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;(in thousands, except for number of investments):&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; white-space: nowrap;" 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; white-space: nowrap;" 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;297&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;323,708&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(553&lt;/div&gt;
        &lt;/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;178,183&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(2,764&lt;/div&gt;
        &lt;/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;501,891&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(3,317&lt;/div&gt;
        &lt;/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;63&lt;/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;199,372&lt;/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;(246&lt;/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;14,777&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%; 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;(386&lt;/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;214,149&lt;/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;(632&lt;/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;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; 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;325,966&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;&#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;(1,031&lt;/div&gt;
        &lt;/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;131,000&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(1,338&lt;/div&gt;
        &lt;/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;456,966&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;&#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;(2,369&lt;/div&gt;
        &lt;/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%; 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;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; 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;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;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;8,352&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; 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;(17&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; 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;7,888&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; 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;(100&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; 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;16,240&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; 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;(117&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: 16%; padding-bottom: 4px; 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;Total temporarily impaired securities&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%; border-bottom: #000000 double 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%; 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;455&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; 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;857,398&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; 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;(1,847&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; 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;331,848&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; 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;(4,588&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; 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;1,189,246&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; 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;(6,435&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;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 rather than underlying credit deterioration for any of the issuers. We believe it is more likely than not that we will be able to hold our debt securities with declines in value to maturity. Therefore, we intend to hold these securities
    to maturity and anticipate full recovery of our debt securities&#x2019; amortized cost basis at maturity.&lt;/div&gt;
</us-gaap:InvestmentTextBlock>
    <us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock
      contextRef="c20230101to20231231"
      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, 2023:&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;68&lt;/div&gt;
        &lt;/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;24&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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;" 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: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(255, 255, 255);" 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%; background-color: rgb(255, 255, 255); border-bottom: 4px double rgb(0, 0, 0); white-space: nowrap;" 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="c20230101to20231231"
      id="Fact_a0389bbbc04d444aa9945a16f2f77b47">P1Y</ions:MaximumContractMaturityPeriodRange1>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage
      contextRef="c20231231"
      decimals="2"
      id="Fact_e1a84f7ba1234915827448c633c10e96"
      unitRef="U003">0.68</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage>
    <ions:MaximumContractMaturityPeriodRange1
      contextRef="c20230101to20231231"
      id="Fact_a9a809b245674eb5912c14df728dc0f0">P1Y</ions:MaximumContractMaturityPeriodRange1>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20230101to20231231"
      id="Fact_d1dd3aa1c3444cc8babea1f02c42cb74">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage
      contextRef="c20231231"
      decimals="2"
      id="Fact_54f16a3082454b16a1368f8660393627"
      unitRef="U003">0.24</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20230101to20231231"
      id="Fact_649df9025a904bcfad6dc6ab6bd4c304">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage
      contextRef="c20231231"
      decimals="2"
      id="Fact_d60e9c8e586b428c886b9d9653ac0f6e"
      unitRef="U003">0.08</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage
      contextRef="c20231231"
      decimals="2"
      id="Fact_298fc5ad20a2442399af2cd8e8215ece"
      unitRef="U003">1</ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage
      contextRef="c20231231"
      decimals="2"
      id="Fact_971b070bcf6846b8970847cdbaef1457"
      unitRef="U003">0.92</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20230101to20231231"
      id="Fact_e4aa3be8fcd040d0bcd0def824af337d">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20231231"
      decimals="INF"
      id="Fact_c487d989afb240aaae9be0536d4b8656"
      unitRef="U007">7</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20231231"
      decimals="INF"
      id="Fact_cc8fa179d30548a7b52fcdc75fe7eeee"
      unitRef="U007">3</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock
      contextRef="c20230101to20231231"
      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, 2023&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;559,967&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;157&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(2,625&lt;/div&gt;
        &lt;/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;557,499&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;224,711&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;64&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;(611&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;224,164&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;513,784&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;152&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(1,889&lt;/div&gt;
        &lt;/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;512,047&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;17,757&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;42&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;(113&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;17,686&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; margin-left: 18pt; 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;1,316,219&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;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;415&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;(5,238&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;1,311,396&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;243,151&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;1,270&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;(692&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;243,729&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;110,138&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;547&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(21&lt;/div&gt;
        &lt;/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;110,664&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;294,873&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;1,239&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;(480&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;295,632&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;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: #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;3,466&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&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;(4&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;3,469&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; margin-left: 18pt; 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: #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;651,628&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;3,063&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;(1,197&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;653,494&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: 27pt; 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: #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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,967,847&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,478&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,435&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,964,890&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;Equity 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;&#160;&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;&#160;&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;&#160;&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;&#160;&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;Publicly traded 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: #CCEEFF;" valign="bottom"&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;11,897&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;236&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(5,832&lt;/div&gt;
        &lt;/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;6,301&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;Privately held 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: #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;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: #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;25,001&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;(5,125&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;42,991&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; margin-left: 18pt; 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: #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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" 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: #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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,237&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,957&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49,292&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; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36pt; 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: #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;
          &lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,002,859&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;&#160;&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,715&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;&#160;&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(17,392&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;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;
          &lt;div style="font-family: 'Times New Roman', Times, 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: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,014,182&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;&#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, 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; margin-left: 18pt; 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; margin-left: 18pt; 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; margin-left: 36pt; 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; 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;Publicly traded 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;Privately held 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; margin-left: 18pt; 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; margin-left: 36pt; 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 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 publicly traded equity securities are included in other current
            assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2023, we recorded a $4.2 million net &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;unrealized loss in our consolidated statements of
              operations related to changes in the fair value of our investments in publicly traded companies.&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;(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 privately held equity securities are included in deposits and other assets. We recognize our privately held 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, which are Level 3 inputs. In the year ended December 31, 2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we recorded a $&lt;/span&gt;2.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million net unrealized gain in our consolidated statements of operations related to changes in the fair value of our investments in privately held companies.&lt;/span&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;&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, 2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;(in thousands, except for number of investments):&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; white-space: nowrap;" 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; white-space: nowrap;" 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;297&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;323,708&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(553&lt;/div&gt;
        &lt;/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;178,183&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(2,764&lt;/div&gt;
        &lt;/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;501,891&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(3,317&lt;/div&gt;
        &lt;/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;63&lt;/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;199,372&lt;/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;(246&lt;/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;14,777&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%; 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;(386&lt;/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;214,149&lt;/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;(632&lt;/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;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; 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;325,966&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;&#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;(1,031&lt;/div&gt;
        &lt;/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;131,000&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(1,338&lt;/div&gt;
        &lt;/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;456,966&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;&#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;(2,369&lt;/div&gt;
        &lt;/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%; 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;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; 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;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;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;8,352&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; 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;(17&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; 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;7,888&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; 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;(100&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; 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;16,240&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; 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;(117&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: 16%; padding-bottom: 4px; 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;Total temporarily impaired securities&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%; border-bottom: #000000 double 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%; 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;455&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; 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;857,398&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; 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;(1,847&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; 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;331,848&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; 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;(4,588&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; 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;1,189,246&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; 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;(6,435&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;


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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. 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;The following tables present the major security types we held at December 31, 2023 and 2022&#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;. 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; white-space: nowrap;" 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, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; white-space: nowrap;" 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; white-space: nowrap;" 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;185,424&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;185,424&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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 (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;801,228&lt;/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;801,228&lt;/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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;334,828&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;334,828&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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 (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;807,679&lt;/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;807,679&lt;/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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,155&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;21,155&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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&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 (5)&lt;/div&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;6,301&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;6,301&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: 4px; background-color: #CCEEFF;" 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; 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;2,156,615&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;999,404&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;1,157,211&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;&#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; white-space: nowrap;" 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; white-space: nowrap;" 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; white-space: nowrap;" 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 (4)&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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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 (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;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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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 (3)&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 (5)&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 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;$33.0 million was included in cash and cash equivalents, 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;(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;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;$11.0 million was included in cash and cash equivalents, 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;(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;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;div style="display:none;"&gt;&lt;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 1.75% Notes, 0% Notes and 0.125% Notes had a fair value of $661.1 million, $667.8 million and $42.4 million at December 31, 2023,
    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="c20230101to20231231"
      id="Text_161f38ed596b48a19876a8584a322dc2">
&lt;div style="display:none;"&gt;&lt;br/&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, 2023 and 2022&#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;. 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; white-space: nowrap;" 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, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; white-space: nowrap;" 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; white-space: nowrap;" 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;185,424&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;185,424&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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 (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;801,228&lt;/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;801,228&lt;/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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;334,828&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;334,828&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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 (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;807,679&lt;/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;807,679&lt;/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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21,155&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;21,155&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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&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 (5)&lt;/div&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;6,301&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;6,301&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: 4px; background-color: #CCEEFF;" 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; 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;2,156,615&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;999,404&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;1,157,211&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;&#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; white-space: nowrap;" 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; white-space: nowrap;" 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; white-space: nowrap;" 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 (4)&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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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 (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;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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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 (3)&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 (5)&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 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;$33.0 million was included in cash and cash equivalents, 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;(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;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;$11.0 million was included in cash and cash equivalents, 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;(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;Included in other current assets 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;7. 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/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;1.75&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;562,285&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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&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;625,380&lt;/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;622,242&lt;/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;&lt;span style="text-indent: 0pt;"&gt;0.125&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;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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;544,504&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;&#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;Liability related to sale of future royalties&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;513,736&lt;/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;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;178,969&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;8,859&lt;/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;8,998&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;/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;33,714&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;7,295&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;/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;1,922,943&lt;/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;1,369,195&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;/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;(8,831&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;(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;/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;1,914,112&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;1,361,660&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;/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 of December 31, 2023, our 0.125%
    Notes was classified as a current liability because it matures in December 2024.&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;1.75%
    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 2023, we completed a $575.0
    million offering of convertible senior notes and used $488.2 million of the net proceeds from the issuance of the 1.75% Notes to repurchase $504.4 million in
    principal of our 0.125% Notes. We expect to use the remaining net proceeds to settle the 0.125% Notes that remain outstanding.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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, 2023, we had the following 1.75%
    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; &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: 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;1.75% 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;575.0&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: 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;12.7&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;&#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_6bfb094eab7041389566a848570cbbe5"&gt;June 2028&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; width: 88%;" 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; 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;1.75&lt;/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: 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;Effective interest rate&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;2.3&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;
          &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: 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;53.73&lt;/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;Total shares of common stock subject to conversion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.7&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;/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;0%
    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 2021, we completed a $632.5
    million offering of convertible senior notes. We used $319.0 million of the net proceeds from the issuance of the 0% Notes to pay the remaining $309.9 million
    principal balance of our 1% Notes 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;At December 31, 2023, 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; &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;7.2&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: 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_77100aa329424b42b6f03dc4fa1e2472"&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; width: 88%;" 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; 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;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: 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;Effective interest rate&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;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: 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 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 &lt;span style="-sec-ix-hidden:Fact_c2c8af8268614a7d9201a587fc5822f5"&gt;April 2026&lt;/span&gt;. The note hedges and warrants are separate transactions and are not part of the terms of our&#160; 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 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%
    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 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of
    our 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;As discussed above, in 2023, we repurchased $504.4
    million of our 0.125% Notes. We are holding the repurchased 0.125% Notes in treasury until maturity. As a result, the remaining principal balance of our 0.125%
    Notes was $44.5 million as of December 31, 2023.
    Additionally, during the year ended December 31, 2023, we recorded a $13.4 million gain on the early retirement of debt, which we recorded as other income in our consolidated statements of operations. The gain on the early retirement of our debt is the difference
    between the amounts paid to repurchase our 0.125% Notes and the net carrying balance of the liability at the time that we completed the
    repurchases.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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, 2023, 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; &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;44.5&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;0.2&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: 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_5c75d58f5a434990850c3cf960d7b0c3"&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; width: 88%;" 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; 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;0.125&lt;/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: 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;Effective interest rate&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;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: 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, excluding shares related to &lt;span style="text-indent: 0pt;"&gt;0.125&lt;/span&gt;% Notes we have repurchased and are currently holding in treasury&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;0.5&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;&#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 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 &lt;/span&gt;&lt;span style="-sec-ix-hidden:Fact_b2783015cbc64323aab97584a4bd55af"&gt;December 2024&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. 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&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 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;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 1.75%, 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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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, 2023, 2022 and 2021 included $5.9 million, $5.3 million and $4.9 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 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 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 2022, we concurrently entered into two
    purchase and sale agreements with a real estate investor. In the same period, we closed the first transaction in which we sold the facilities at our headquarters in Carlsbad, California, which includes our primary R&amp;amp;D facility, for a purchase price
    of $263.4 million. As a result, 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 in our consolidated statements of operations. 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. In connection with this transaction, we leased back
    our headquarters facilities for an initial lease term of 15 years with options to extend the lease for two additional terms of five years each.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 August 2023, we closed the second transaction and transferred legal ownership of two lots of undeveloped land adjacent to our headquarters to the real estate investor for a purchase price of $33 million. In connection with this transaction, we entered into a build-to-suit lease agreement with the same real estate investor to lease a new R&amp;amp;D facility. The lessor will develop and
    construct a new building composed of R&amp;amp;D and office 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 15 years with options to extend the lease for two additional terms of five years each. The lease will commence once the structure of this new facility is completed.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Since the building is under construction and unavailable to lease, we are unable to complete the sale-leaseback evaluation under ASC 842,
    Leases. As a result, the land remains in our consolidated balance sheets and we accounted for the proceeds as a financial liability. We will reassess the transaction under the sale-leaseback accounting guidance when the facilities are available for
    lease commencement.&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, 2023 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;2024&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;55,298&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;2025&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;10,657&lt;/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;2026&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;643,157&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;2027&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;10,509&lt;/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;2028&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;580,277&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;8,462&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;1,308,360&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: 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;(157&lt;/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;(47,138&lt;/div&gt;
        &lt;/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;(20,061&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 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;1,241,004&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: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&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. 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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 upfront payment of $500
    million as a liability related to the sale of future royalties, net of transaction costs of $10.4 million, which we are amortizing over the
    estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty
    Pharma as a reduction of the liability.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 determine the effective interest rate used to record
      interest expense under this agreement based on an estimate of future royalty payments to Royalty Pharma. As of &lt;/span&gt;December 31, 2023&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the estimated effective interest rate under the agreement was &lt;/span&gt;13.5 percent&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following is a summary of our liability related to
      sale of future royalties for the year ended &lt;/span&gt;December 31, 2023&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: 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;Proceeds from sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;500,000&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;Royalty payments to Royalty Pharma&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;(44,628&lt;/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: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense related to sale of future royalties&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;68,238&lt;/div&gt;
        &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;/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;Liability related to sale of future royalties as of December 31, 2023&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;523,610&lt;/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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Issuance costs related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,434&lt;/div&gt;
        &lt;/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: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amortization of issuance costs related to sale of future royalties as of December 31, 2023&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;560&lt;/div&gt;
        &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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net liability related to sale of future royalties as of December 31, 2023&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;513,736&lt;/div&gt;
        &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;&#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;There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty
    payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the commercial sales of SPINRAZA, the regulatory approval and commercial sales of
    pelacarsen, competing products or other significant events.&lt;/div&gt;
</us-gaap:DebtDisclosureTextBlock>
    <us-gaap:ScheduleOfDebtInstrumentsTextBlock
      contextRef="c20230101to20231231"
      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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/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;1.75&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;562,285&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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&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;625,380&lt;/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;622,242&lt;/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;&lt;span style="text-indent: 0pt;"&gt;0.125&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;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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;544,504&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;&#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;Liability related to sale of future royalties&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;513,736&lt;/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;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;178,969&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;8,859&lt;/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;8,998&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;/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;33,714&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;7,295&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;/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;1,922,943&lt;/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;1,369,195&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;/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;(8,831&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;(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;/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;1,914,112&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;1,361,660&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;/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, 2023, we had the following 1.75%
    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; &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: 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;1.75% 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;575.0&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: 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;12.7&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;&#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_6bfb094eab7041389566a848570cbbe5"&gt;June 2028&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; width: 88%;" 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; 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;1.75&lt;/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: 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;Effective interest rate&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;2.3&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;
          &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: 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;53.73&lt;/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;Total shares of common stock subject to conversion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.7&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;/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;At December 31, 2023, 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; &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;7.2&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: 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_77100aa329424b42b6f03dc4fa1e2472"&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; width: 88%;" 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; 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;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: 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;Effective interest rate&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;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: 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;
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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, 2023, 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; &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;44.5&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;0.2&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: 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;
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    &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_5c75d58f5a434990850c3cf960d7b0c3"&gt;December 2024&lt;/span&gt;&lt;/div&gt;
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    &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;Interest rate&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;0.125&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;

  &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;Effective interest rate&lt;/div&gt;
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    &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;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: 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, excluding shares related to &lt;span style="text-indent: 0pt;"&gt;0.125&lt;/span&gt;% Notes we have repurchased and are currently holding in treasury&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;0.5&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;&#160;&lt;/td&gt;

  &lt;/tr&gt;


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      id="Fact_e1b424eff905493698bc9b6f4316f08f"
      unitRef="U001">150100000</us-gaap:GainLossOnDispositionOfAssets1>
    <us-gaap:RepaymentsOfSecuredDebt
      contextRef="c20220101to20221231_DebtInstrumentAxis_PrimaryResearchAndDevelopmentFacilityMortgageMember"
      decimals="-5"
      id="Fact_ee22c79230e54d5289dec6e7979e0722"
      unitRef="U001">51300000</us-gaap:RepaymentsOfSecuredDebt>
    <us-gaap:LesseeOperatingLeaseTermOfContract
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember"
      id="Fact_e6d37e165f84425ea9db0bd0fa02c2cf">P15Y</us-gaap:LesseeOperatingLeaseTermOfContract>
    <ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember"
      decimals="INF"
      id="Fact_0746b48df37641eaab4f8443ed332073"
      unitRef="U020">2</ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease>
    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember"
      id="Fact_693e91d48d5b4feebec724ed9ff884f7">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <ions:NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor
      contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_LandMember"
      decimals="INF"
      id="Fact_a8c5588ea2e04cc99ff52c8cb117bb7b"
      unitRef="U019">2</ions:NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor>
    <us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment
      contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_LandMember"
      decimals="-6"
      id="Fact_c3af5a38042e409fa61183221c638107"
      unitRef="U001">33000000</us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment>
    <us-gaap:LesseeOperatingLeaseTermOfContract
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_NewResearchAndDevelopmentFacilityInCarlsbadCAMember"
      id="Fact_e198dab14cc74d2fadbd634160d04423">P15Y</us-gaap:LesseeOperatingLeaseTermOfContract>
    <ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_NewResearchAndDevelopmentFacilityInCarlsbadCAMember"
      decimals="INF"
      id="Fact_23a41853ffc14bdb96e6c3de4058ab3a"
      unitRef="U020">2</ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease>
    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_NewResearchAndDevelopmentFacilityInCarlsbadCAMember"
      id="Fact_782a866aae5e44f4a70dc6a5aa6bd1b5">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <srt:ContractualObligationFiscalYearMaturityScheduleTableTextBlock
      contextRef="c20230101to20231231"
      id="Text_16539426e6924191b5cc465550dba8af">
&lt;div style="display:none;"&gt;&lt;br/&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, 2023 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;2024&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;55,298&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;2025&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;10,657&lt;/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;2026&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;643,157&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;2027&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;10,509&lt;/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;2028&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;580,277&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;8,462&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;1,308,360&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: 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;(157&lt;/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;(47,138&lt;/div&gt;
        &lt;/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;(20,061&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 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;1,241,004&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="c20231231"
      decimals="-3"
      id="Fact_d2eb54062a6d4f188ef1dbae3b8653d3"
      unitRef="U001">55298000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo
      contextRef="c20231231"
      decimals="-3"
      id="Fact_c42e928b65cd45aa923675e567769ac7"
      unitRef="U001">10657000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree
      contextRef="c20231231"
      decimals="-3"
      id="Fact_6b7eb3455bef4825bec5934f0ca8a9f2"
      unitRef="U001">643157000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour
      contextRef="c20231231"
      decimals="-3"
      id="Fact_5163088d8dfb4bd8afb6a945c3e15b83"
      unitRef="U001">10509000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive
      contextRef="c20231231"
      decimals="-3"
      id="Fact_04194527fb664e52a3ac79595e34b654"
      unitRef="U001">580277000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive
      contextRef="c20231231"
      decimals="-3"
      id="Fact_74f3f2a83bb64af5b0b4b21df7d35ef0"
      unitRef="U001">8462000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive>
    <us-gaap:LongTermDebt
      contextRef="c20231231"
      decimals="-3"
      id="Fact_41f58f8c96774a38af7b7c1cc41eabb9"
      unitRef="U001">1308360000</us-gaap:LongTermDebt>
    <us-gaap:LongTermDebtCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_bc879ac3c37f49de90a976632193e86e"
      unitRef="U001">157000</us-gaap:LongTermDebtCurrent>
    <us-gaap:InterestPayableCurrentAndNoncurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_ef9db53e88e14db9b13d2afa08b9cc23"
      unitRef="U001">47138000</us-gaap:InterestPayableCurrentAndNoncurrent>
    <us-gaap:DeferredFinanceCostsNet
      contextRef="c20231231"
      decimals="-3"
      id="Fact_97e59891cc4a4a90baf9d56b32982707"
      unitRef="U001">20061000</us-gaap:DeferredFinanceCostsNet>
    <us-gaap:LongTermDebtNoncurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_2e8033307b594b4f9b2e30ee6ba95bc3"
      unitRef="U001">1241004000</us-gaap:LongTermDebtNoncurrent>
    <us-gaap:LesseeOperatingLeasesTextBlock
      contextRef="c20230101to20231231"
      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 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 an additional office space and warehouse space in Carlsbad. We lease these spaces under non-cancelable operating leases. In
    2022, we exercised our option to extend the office space lease, extending our term from January 2023 to May 2027. We have no remaining options
    to extend this lease. Our warehouse space lease in Carlsbad has an initial term ending in 2028 with no options to extend the 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;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 2022. 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. 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
    transfer of legal ownership of the two lots of undeveloped land to the real estate investor, we entered 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. The lease will commence once the structure of this new facility is completed.&lt;/div&gt;

&lt;div&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 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility to be constructed by
    the lessor in Oceanside, California. We capitalized costs that we incurred related to the design and development of tenant improvements as construction-in-progress in our consolidated balance sheets. In August 2023, we reached a mutual agreement with
    the lessor to terminate the lease agreement. As a result, we recorded a charge of $20 million, primarily associated with the impairment of
    construction-in-progress assets, within &lt;span style="-sec-ix-hidden:Fact_ebdf1ed5cf6845079198439e7c520f42"&gt;SG&amp;amp;A expense&lt;/span&gt; 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; 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 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 in January 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 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 in November 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; white-space: nowrap;" 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, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;171.9&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: 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;179.0&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;&#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;13.0 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, 2023,
    2022, and 2021 we paid $20.1 million, $4.0 million and $3.3 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, 2023,
    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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" 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;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;20,398&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;2025&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;20,645&lt;/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;2026&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;20,781&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;2027&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;20,800&lt;/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;2028&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,774&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;176,138&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;279,536&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(100,567&lt;/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;(8,094&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;170,875&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 $23.1 million,
    $8.3 million and $3.4 million for the
    years ended December 31, 2023, 2022
    and 2021, respectively. &lt;/div&gt;
</us-gaap:LesseeOperatingLeasesTextBlock>
    <ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadFacilityMember"
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      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadOfficeSpaceMember"
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      id="Fact_08797d9de1754a398e2476e465a5a05d"
      unitRef="U020">0</ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease>
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      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember"
      id="Fact_7f2058c8172e474bbf205fda14546132">P15Y</us-gaap:LesseeOperatingLeaseTermOfContract>
    <ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember"
      decimals="INF"
      id="Fact_2ee2e32f70634bcfa6b92ccee44f0bdf"
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    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember"
      id="Fact_1488c1954cd849a1a4f6161cf2b82691">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember"
      decimals="-6"
      id="Fact_a1b244754eec475a945bcce4913ec530"
      unitRef="U001">280000000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue>
    <ions:NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor
      contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember"
      decimals="INF"
      id="Fact_17aadca36cd14bb7b824374f744e4abc"
      unitRef="U019">2</ions:NumberOfLotsOfUndevelopedLandTransferredToRealEstateInvestor>
    <us-gaap:ImpairmentOfLongLivedAssetsHeldForUse
      contextRef="c20230801to20230831_PropertyPlantAndEquipmentByTypeAxis_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember"
      decimals="-6"
      id="Fact_171f16cc89494c4ea4ec3ca4d9a325d8"
      unitRef="U001">20000000</us-gaap:ImpairmentOfLongLivedAssetsHeldForUse>
    <us-gaap:LesseeOperatingLeaseTermOfContract
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember"
      id="Fact_1cf767bfa2604645b03665b44c8069bb">P123M</us-gaap:LesseeOperatingLeaseTermOfContract>
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      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember"
      id="Fact_c9d11c93abf3409aab88ca3e2efcb6a1">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <ions:LesseeOperatingLeasePeriodOfFreeRent
      contextRef="c20230101to20231231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember"
      id="Fact_ba6fa8c8bcc140258a36c6828c2ab217">P3M</ions:LesseeOperatingLeasePeriodOfFreeRent>
    <us-gaap:LessorOperatingLeaseTermOfContract
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember"
      id="Fact_f3673b6f6d8a469cb3fc9b19fe6c9445">P83M</us-gaap:LessorOperatingLeaseTermOfContract>
    <ions:LessorOperatingLeaseNumberOfOptionsToExtendLease
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember"
      decimals="INF"
      id="Fact_8c1775b36c92469e9d8ba3d06078efc9"
      unitRef="U020">0</ions:LessorOperatingLeaseNumberOfOptionsToExtendLease>
    <ions:LessorOperatingLeasePeriodOfFreeRent
      contextRef="c20230101to20231231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember"
      id="Fact_bdb3d42dbeaf484494c12e827a769a24">P7M</ions:LessorOperatingLeasePeriodOfFreeRent>
    <us-gaap:LessorOperatingLeasePaymentsToBeReceived
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember"
      decimals="-5"
      id="Fact_7c8de04d910848adb798d3e411c0825d"
      unitRef="U001">9600000</us-gaap:LessorOperatingLeasePaymentsToBeReceived>
    <us-gaap:LesseeOperatingLeaseTermOfContract
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      id="Fact_f252e6bc1ca849dfb22869bd4a71369a">P91M</us-gaap:LesseeOperatingLeaseTermOfContract>
    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      id="Fact_093b7e88a1474547a8fe7129936aa7cd">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <ions:LesseeOperatingLeasePeriodOfFreeRent
      contextRef="c20230101to20231231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      id="Fact_99931a7181e04c71bbd9180a5f64f952">P7M</ions:LesseeOperatingLeasePeriodOfFreeRent>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue
      contextRef="c20231231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      decimals="-5"
      id="Fact_c350c485d2194852998ea1b496903ff5"
      unitRef="U001">6800000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue>
    <ions:LesseeOperatingLeaseInformationTableTextBlock
      contextRef="c20230101to20231231"
      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; white-space: nowrap;" 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, 2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;171.9&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: 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;179.0&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;&#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;13.0 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="c20231231"
      decimals="-5"
      id="Fact_42b72db309654cf1bdbfe546a3a2176d"
      unitRef="U001">171900000</us-gaap:OperatingLeaseRightOfUseAsset>
    <us-gaap:OperatingLeaseLiability
      contextRef="c20231231"
      decimals="-5"
      id="Fact_44caa1523d334df48c7b2561738097e4"
      unitRef="U001">179000000</us-gaap:OperatingLeaseLiability>
    <us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1
      contextRef="c20231231"
      id="Fact_ccfd1bbd8568445fb43b6a1d85973cc7">P13Y</us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1>
    <us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent
      contextRef="c20231231"
      decimals="3"
      id="Fact_0f6726aa9c174130a3010b4dad4799ef"
      unitRef="U003">0.069</us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent>
    <us-gaap:OperatingLeasePayments
      contextRef="c20230101to20231231"
      decimals="-5"
      id="Fact_826cead5743b4e90a9d8b807e97fe422"
      unitRef="U001">20100000</us-gaap:OperatingLeasePayments>
    <us-gaap:OperatingLeasePayments
      contextRef="c20220101to20221231"
      decimals="-5"
      id="Fact_297fcce7f2e44b348fe63e7be360cf7c"
      unitRef="U001">4000000</us-gaap:OperatingLeasePayments>
    <us-gaap:OperatingLeasePayments
      contextRef="c20210101to20211231"
      decimals="-5"
      id="Fact_50e928616e964a8c94f28d1e4409995c"
      unitRef="U001">3300000</us-gaap:OperatingLeasePayments>
    <us-gaap:LesseeOperatingLeaseLiabilityMaturityTableTextBlock
      contextRef="c20230101to20231231"
      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, 2023,
    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; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" 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;2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;20,398&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;2025&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;20,645&lt;/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;2026&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;20,781&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;2027&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;20,800&lt;/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;2028&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,774&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;176,138&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;279,536&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(100,567&lt;/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;(8,094&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;170,875&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="c20231231"
      decimals="-3"
      id="Fact_9240bc8118ea402f85a2119c7486d19d"
      unitRef="U001">20398000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo
      contextRef="c20231231"
      decimals="-3"
      id="Fact_4609f99ef9604c9aae3baed51a3c3fed"
      unitRef="U001">20645000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearThree
      contextRef="c20231231"
      decimals="-3"
      id="Fact_d11239309f5945a3891ef526d1491daa"
      unitRef="U001">20781000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearThree>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFour
      contextRef="c20231231"
      decimals="-3"
      id="Fact_43a6c7550e004272b7f9ca99a8ba22d8"
      unitRef="U001">20800000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFour>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFive
      contextRef="c20231231"
      decimals="-3"
      id="Fact_74899d789ebf4c2ebccd545b74c63e21"
      unitRef="U001">20774000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFive>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive
      contextRef="c20231231"
      decimals="-3"
      id="Fact_3931369a624044a9b1905cb93b92544f"
      unitRef="U001">176138000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue
      contextRef="c20231231"
      decimals="-3"
      id="Fact_3603a725690b46dda9be3db4e21043c4"
      unitRef="U001">279536000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue>
    <us-gaap:LesseeOperatingLeaseLiabilityUndiscountedExcessAmount
      contextRef="c20231231"
      decimals="-3"
      id="Fact_6d8e7a3e7ccb4ac9a37ea341d9cadf8c"
      unitRef="U001">100567000</us-gaap:LesseeOperatingLeaseLiabilityUndiscountedExcessAmount>
    <us-gaap:OperatingLeaseLiabilityCurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_599739bca7c14726b6810c3c3a59fcff"
      unitRef="U001">8094000</us-gaap:OperatingLeaseLiabilityCurrent>
    <us-gaap:OperatingLeaseLiabilityNoncurrent
      contextRef="c20231231"
      decimals="-3"
      id="Fact_5bc4a22d2bca49aca884201dc1170194"
      unitRef="U001">170875000</us-gaap:OperatingLeaseLiabilityNoncurrent>
    <us-gaap:OperatingLeaseExpense
      contextRef="c20230101to20231231"
      decimals="-5"
      id="Fact_b625c294a3bd434f8c74620b51e1ea20"
      unitRef="U001">23100000</us-gaap:OperatingLeaseExpense>
    <us-gaap:OperatingLeaseExpense
      contextRef="c20220101to20221231"
      decimals="-5"
      id="Fact_37e7125f4da2437a81d1b7f1853e4554"
      unitRef="U001">8300000</us-gaap:OperatingLeaseExpense>
    <us-gaap:OperatingLeaseExpense
      contextRef="c20210101to20211231"
      decimals="-5"
      id="Fact_a6f37ce5e1654e67b6bfb04f2bfaa94b"
      unitRef="U001">3400000</us-gaap:OperatingLeaseExpense>
    <ions:UpfrontRoyaltyPaymentReceived
      contextRef="c20230101to20230131"
      decimals="-6"
      id="Fact_c8ba625af5db4c629715e10efedcdff1"
      unitRef="U001">500000000</ions:UpfrontRoyaltyPaymentReceived>
    <ions:MaximumAmountOfPaymentsReceivableForAdditionalMilestones
      contextRef="c20230131"
      decimals="-6"
      id="Fact_d5508d985dec4c9299c67fd453890fd5"
      unitRef="U001">625000000</ions:MaximumAmountOfPaymentsReceivableForAdditionalMilestones>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember"
      decimals="2"
      id="Fact_04d45df1075f4c7282dba5c75f87090a"
      unitRef="U003">0.25</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember"
      decimals="2"
      id="Fact_7db57813067c495a9024650b8968a999"
      unitRef="U003">0.45</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid
      contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember"
      decimals="-8"
      id="Fact_9f09740d482b4450bde402e99f9264a9"
      unitRef="U001">1500000000</ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20230131_ProductOrServiceAxis_PelacarsenMember"
      decimals="2"
      id="Fact_4f14fcd874cc407499d3f48e153e6244"
      unitRef="U003">0.25</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack
      contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember"
      decimals="-6"
      id="Fact_2203af9e770d4ee987086d61868bd2ee"
      unitRef="U001">475000000</ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack>
    <ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack
      contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember"
      decimals="-6"
      id="Fact_dcfdc1338630420c9019168b9412101d"
      unitRef="U001">550000000</ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack>
    <ions:UpfrontRoyaltyPaymentReceived
      contextRef="c20230101to20230131"
      decimals="-6"
      id="Fact_f0e73629c96a44169a5a0e9d8a1d4b9a"
      unitRef="U001">500000000</ions:UpfrontRoyaltyPaymentReceived>
    <ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-5"
      id="Fact_1391ba32fa9a456194c1aa68413d1b61"
      unitRef="U001">10400000</ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="3"
      id="Fact_d7d548cc748640208f68b9bf1f4a17e2"
      unitRef="U003">0.135</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:OtherNoncurrentLiabilitiesTableTextBlock
      contextRef="c20230101to20231231"
      id="Text_21736a72e1aa4319a1ee1097952860ac">
&lt;div style="display:none;"&gt;&lt;br/&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 liability related to
      sale of future royalties for the year ended &lt;/span&gt;December 31, 2023&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: 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;Proceeds from sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;500,000&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;Royalty payments to Royalty Pharma&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;(44,628&lt;/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: top; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense related to sale of future royalties&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;68,238&lt;/div&gt;
        &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;/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;Liability related to sale of future royalties as of December 31, 2023&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;523,610&lt;/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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Issuance costs related to sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,434&lt;/div&gt;
        &lt;/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: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amortization of issuance costs related to sale of future royalties as of December 31, 2023&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;560&lt;/div&gt;
        &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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net liability related to sale of future royalties as of December 31, 2023&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;513,736&lt;/div&gt;
        &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;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:OtherNoncurrentLiabilitiesTableTextBlock>
    <ions:ProceedsFromSaleOfFutureRoyalties
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_b900ad354383483f9c34ba3b6c879d07"
      unitRef="U001">500000000</ions:ProceedsFromSaleOfFutureRoyalties>
    <ions:RoyaltyPayments
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_67ccd0c0a7a24a5f910faba6121087a7"
      unitRef="U001">44628000</ions:RoyaltyPayments>
    <ions:InterestExpenseRelatedToSaleOfFutureRoyalties
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_a9cc1712c3f242eb9a739d51e13366c1"
      unitRef="U001">68238000</ions:InterestExpenseRelatedToSaleOfFutureRoyalties>
    <ions:LiabilityRelatedToSaleOfFutureRoyaltiesGross
      contextRef="c20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_421502ea384841d691af85563752cb84"
      unitRef="U001">523610000</ions:LiabilityRelatedToSaleOfFutureRoyaltiesGross>
    <ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_1644e2bd10d14c018b1fdb09c827c31a"
      unitRef="U001">10434000</ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties>
    <ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_99010a2025d14f9695d7f43cbc7feb2d"
      unitRef="U001">560000</ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties>
    <ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet
      contextRef="c20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_c74c6b7b6d844b66867bedb3fe98aa1a"
      unitRef="U001">513736000</ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet>
    <us-gaap:StockholdersEquityNoteDisclosureTextBlock
      contextRef="c20230101to20231231"
      id="Text_334061329e6345ae91c6341ea13083ef">
&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;8. 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, 2023, 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, 2023.&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, 2023 and 2022, we had 300 million shares of common
    stock authorized, of which 144.3 million and 142.1 million were issued and outstanding, respectively. As of December 31, 2023,
    total common shares reserved for future issuance were 49.7 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, 2023,
    2022 and 2021, we issued 2.3 million, 1.2 million and 1.1 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 $49.4 million, $6.4
    million and $11.6 million in 2023,
    2022 and 2021, 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;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 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 Stock Option Plan, or 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 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. At December 31, 2023, no options were outstanding and 68,000 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 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 June 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;In June 2023, 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 to increase the total number of shares of common stock
      authorized for issuance under the 2011 Plan from &lt;/span&gt;29.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;
      million to &lt;/span&gt;35.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million.&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 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, 2023, a total of 12.8 million
    options were outstanding, of which 8.7 million were exercisable, 3.3 million restricted stock unit awards were outstanding, and 8.0 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 2020, we assumed the
      unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In 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, 2023, a total of 0.4 million
    options were outstanding, of which 0.1 million were exercisable, 0.2 million restricted stock unit awards were outstanding, and 1.0 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&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&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&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&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&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&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 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 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 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&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&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&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&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, 2023, a total of 0.9 million options were outstanding, of which 0.9 million were exercisable, 40,000 restricted stock unit awards were outstanding, and 0.5
    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 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, 2023. The ESPP
    permits full-time employees to purchase common stock through payroll deductions (which cannot exceed 10 percent of each employee&#x2019;s compensation)
    at the lower of 85 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 six months from the date of purchase. During 2023, employees purchased and we issued to employees 0.1
    million shares under the ESPP at a weighted average price of $30.53 per share. At December 31, 2023, there were 0.4 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, 2023 (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; white-space: nowrap;" 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; white-space: nowrap;" 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; white-space: nowrap;" 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; white-space: nowrap;" 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, 2022&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;14,970&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;50.57&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;2,407&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;38.80&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;(1,444&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;45.06&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;(1,842&lt;/div&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;55.90&lt;/div&gt;
        &lt;/td&gt;

    &lt;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, 2023&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;14,091&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;48.43&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;4.74&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;78,542&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, 2023&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;9,703&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;52.24&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;3.20&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;28,349&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 $19.72, $18.66 and $24.35 for the years ended December 31, 2023, 2022 and 2021, respectively. The total intrinsic value of options
    exercised during the years ended December 31, 2023, 2022 and 2021 were $6.0 million, $1.4 million and $2.5 million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $65.1 million, $3.6 million and $8.5 million for the years ended December 31, 2023, 2022 and 2021, respectively. For the year
    ended December 31, 2023, the weighted-average fair value of options exercised was $49.23. As of December 31, 2023, total unrecognized compensation cost related to
    non-vested stock options was $36.6 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, 2023 (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; white-space: nowrap;" 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, 2022&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;2,766&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;48.30&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;1,707&lt;/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;40.51&lt;/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;(1,055&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;
          &lt;div style="font-family: 'Times 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;51.64&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;&#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;(179&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;42.90&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, 2023&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;3,239&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;43.40&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, 2023,
    2022 and 2021, the
    weighted-average grant date fair value of RSUs granted was $40.51, $36.14 and $57.02 per RSU, respectively. As of December 31, 2023, total unrecognized compensation cost related to RSUs was $53.7 million. We expect to recognize this cost over a weighted average period of 1.3
    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, 2023 (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; white-space: nowrap;" 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, 2022&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;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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;52.59&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: 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;158&lt;/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;57.43&lt;/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: 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%; 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;(75&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%; padding-bottom: 2px; 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: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52.43&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; 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, 2023&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;226&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;56.04&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;For the years ended December 31, 2023,
    2022 and 2021, the
    weighted-average grant date fair value of PRSUs granted was $57.43, $42.28 and $77.17 per PRSU, respectively. As of December 31, 2023, total unrecognized compensation cost related to PRSUs was $4.4 million. We expect to recognize this cost over a weighted average period of 1.4
    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, 2023, 2022 and 2021 (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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;499&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;77,826&lt;/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;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;/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;27,484&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;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;/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;105,809&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;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;/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;Refer to 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, 2023,
    2022 and 2021, 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;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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;3.8&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;46.8&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;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;/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;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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;3.8&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;52.7&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;
          &lt;div style="font-family: 'Times 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;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;/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;7.7 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;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;/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;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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;5.3&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;
          &lt;div style="font-family: 'Times 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;0.1&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;/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;36.0&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;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;/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 years ended December 31, 2023 and 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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      id="Fact_199329985b3f4b9a93a30c0aba085d4e"
      unitRef="U002">150000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized
      contextRef="c20231231_PlanNameAxis_EmployeeStockPurchasePlanMember"
      decimals="-5"
      id="Fact_38cefc5306ef4b91b96aa796ece9f65c"
      unitRef="U002">3200000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized>
    <us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate
      contextRef="c20231231_PlanNameAxis_EmployeeStockPurchasePlanMember"
      decimals="2"
      id="Fact_cde6d0b8308541d399ef173d781f45db"
      unitRef="U003">0.10</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate>
    <us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent
      contextRef="c20230101to20231231_PlanNameAxis_EmployeeStockPurchasePlanMember"
      decimals="2"
      id="Fact_194baea1b26142beaba2816576b72b95"
      unitRef="U003">0.85</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent>
    <ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod
      contextRef="c20230101to20231231_PlanNameAxis_EmployeeStockPurchasePlanMember"
      id="Fact_c0a6d71bb09f40b8b835538d12005c8d">P6M</ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod>
    <us-gaap:StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans
      contextRef="c20230101to20231231_PlanNameAxis_EmployeeStockPurchasePlanMember"
      decimals="-5"
      id="Fact_28531580c1b34f999f1b8c754d078864"
      unitRef="U002">100000</us-gaap:StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans>
    <ions:EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased
      contextRef="c20230101to20231231_PlanNameAxis_EmployeeStockPurchasePlanMember"
      decimals="2"
      id="Fact_19161be6484c4f6f96fdfb2dbfaf9342"
      unitRef="U004">30.53</ions:EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased>
    <ions:EmployeeStockPurchasePlanSharesAvailableForPurchase
      contextRef="c20231231_PlanNameAxis_EmployeeStockPurchasePlanMember"
      decimals="-5"
      id="Fact_d43712676b7c40d4972a35e470cb8c41"
      unitRef="U002">400000</ions:EmployeeStockPurchasePlanSharesAvailableForPurchase>
    <us-gaap:ScheduleOfShareBasedCompensationStockOptionsActivityTableTextBlock
      contextRef="c20230101to20231231"
      id="Text_b08686db7e214f558296c6c15bcdf2af">
&lt;div style="display:none;"&gt;&lt;br/&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, 2023 (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; white-space: nowrap;" 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; white-space: nowrap;" 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; white-space: nowrap;" 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; white-space: nowrap;" 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, 2022&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;14,970&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;50.57&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;2,407&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;38.80&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;(1,444&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;45.06&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;(1,842&lt;/div&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;55.90&lt;/div&gt;
        &lt;/td&gt;

    &lt;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, 2023&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;14,091&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;48.43&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;4.74&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;78,542&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, 2023&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;9,703&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;52.24&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;3.20&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;28,349&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, 2023 (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; white-space: nowrap;" 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, 2022&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;2,766&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;48.30&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;1,707&lt;/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;40.51&lt;/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;(1,055&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;
          &lt;div style="font-family: 'Times 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;51.64&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;&#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;(179&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;42.90&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, 2023&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;3,239&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;43.40&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, 2023 (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; white-space: nowrap;" 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, 2022&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;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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;52.59&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: 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;158&lt;/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;57.43&lt;/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: 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%; 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;(75&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%; padding-bottom: 2px; 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: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52.43&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; 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, 2023&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;226&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;56.04&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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      unitRef="U004">77.17</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions
      contextRef="c20231231_AwardTypeAxis_PerformanceSharesMember"
      decimals="-5"
      id="Fact_55da732e82574a34abe4222633cd4e1e"
      unitRef="U001">4400000</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions>
    <us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1
      contextRef="c20230101to20231231_AwardTypeAxis_PerformanceSharesMember"
      id="Fact_21013d0b3fbf4c7d8cb5b038888e55b6">P1Y4M24D</us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1>
    <us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock
      contextRef="c20230101to20231231"
      id="Text_bd65770233d04dc19e93bdd16a5dbb30">
&lt;div style="display:none;"&gt;&lt;br/&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, 2023, 2022 and 2021 (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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;499&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;77,826&lt;/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;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;/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;27,484&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;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;/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;105,809&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;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;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20230101to20231231_IncomeStatementLocationAxis_CostOfSalesMember"
      decimals="-3"
      id="Fact_c65bd9300b1849b09ce0cf552755ec1d"
      unitRef="U001">499000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20220101to20221231_IncomeStatementLocationAxis_CostOfSalesMember"
      decimals="-3"
      id="Fact_5192811678f84304b2c63cedee948433"
      unitRef="U001">533000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20210101to20211231_IncomeStatementLocationAxis_CostOfSalesMember"
      decimals="-3"
      id="Fact_a370ff2076d840e78591c1b614a65c61"
      unitRef="U001">456000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20230101to20231231_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember"
      decimals="-3"
      id="Fact_082a856e25ff4c6c87bb43e07011a3a0"
      unitRef="U001">77826000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20220101to20221231_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember"
      decimals="-3"
      id="Fact_fbf019d0d38c4d20951785656bdfb76e"
      unitRef="U001">73704000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20210101to20211231_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentMember"
      decimals="-3"
      id="Fact_590dd7d3580e4ce79e0bd853a27c60e2"
      unitRef="U001">87522000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20230101to20231231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember"
      decimals="-3"
      id="Fact_faf4608623c94854a015ec45e8a2e44a"
      unitRef="U001">27484000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20220101to20221231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember"
      decimals="-3"
      id="Fact_e2891cabb204471380d6c8707ca7c311"
      unitRef="U001">26027000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20210101to20211231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember"
      decimals="-3"
      id="Fact_1d43b8c463a34284a11803d822ccf283"
      unitRef="U001">32700000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_e526ced9a8ee48df88cdbb0fe414de86"
      unitRef="U001">105809000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_e09ed4e35f1149ffade548f4d1e3dd6a"
      unitRef="U001">100264000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:AllocatedShareBasedCompensationExpense
      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_14e48c9e15754897b6ddb6e8ce984ffb"
      unitRef="U001">120678000</us-gaap:AllocatedShareBasedCompensationExpense>
    <us-gaap:ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock
      contextRef="c20230101to20231231"
      id="Text_7c5c98a925664a98af16333c600a4036">
&lt;div style="display:none;"&gt;&lt;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;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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;3.8&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;46.8&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;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;/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;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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;3.8&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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;/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;52.7&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;
          &lt;div style="font-family: 'Times 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;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;/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;7.7 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;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;/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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;5.3&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;
          &lt;div style="font-family: 'Times 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;0.1&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;/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;36.0&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;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;/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;


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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;9. 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;(334,707&lt;/div&gt;
        &lt;/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;(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;/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;742&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;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;/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;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;(333,965&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;(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;/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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;" 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;35,861&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;(3,687&lt;/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;1,129&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;/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;147&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;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;/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;32,321&lt;/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;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;/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;&#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%; 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;&#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: -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;32,321&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;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;/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;"&gt;Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to loss before income 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;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;/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 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;(333,965&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;(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;/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;(70,133&lt;/div&gt;
        &lt;/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;(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;/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;(22,597&lt;/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;6.8&lt;/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;(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;/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;(22&lt;/div&gt;
        &lt;/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;(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;/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;175,388&lt;/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;(52.5&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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;/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;&#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;/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;(67,131&lt;/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;20.1&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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;/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;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;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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;(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;/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;1,023&lt;/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;(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;/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;3,814&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(1.1&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;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;/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;327&lt;/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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;/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;Foreign-derived intangible income benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,493&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;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.2&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;&#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;&#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; 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;19,546&lt;/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;(5.9&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;14,030&lt;/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;(5.4&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;4,720&lt;/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;(16.2&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;/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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(405&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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;" 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: 4px double rgb(0, 0, 0);" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, 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: 4px double rgb(0, 0, 0);" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,321&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: 4px double rgb(0, 0, 0);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times 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: 4px double rgb(0, 0, 0);" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, 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: 4px double rgb(0, 0, 0);" 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: 4px double rgb(0, 0, 0);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" 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%; border-bottom: 4px double rgb(0, 0, 0); white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times 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: 4px double rgb(0, 0, 0);" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, 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: 4px double rgb(0, 0, 0);" 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: 4px double rgb(0, 0, 0);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0);" 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%; border-bottom: 4px double rgb(0, 0, 0); white-space: nowrap;" 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, 2023 and 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; 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/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;77,964&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;239,962&lt;/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;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;/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;71,683&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;77,468&lt;/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;86,983&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;/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;104,380&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;104,649&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;/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;16,849&lt;/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;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;/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;Capitalized research and development 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;238,738&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;119,635&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;Long-term 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;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,718&lt;/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;45,612&lt;/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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;144,608&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;10,343&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;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;/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;1,025,713&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;(4,166&lt;/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;(4,475&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;/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;(42,007&lt;/div&gt;
        &lt;/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;(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;/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;(1,910&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;(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;/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;977,630&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;(977,630&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;(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;/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 $169
    million from December 31, 2022 to December 31, 2023.
    The increase was primarily related to increases in our deferred tax assets for capitalized research and development expenses and sale of future 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;At December 31, 2023, we had
    federal and state, primarily California, tax net operating loss carryforwards of $242.8 million and $398.8 million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2032. At December 31, 2023, we also had federal and California research and development tax credit carryforwards of $169.7 million and $124.4 million, respectively. Our federal research and development
    tax credit carryforwards will begin to expire in 2038. Our California research and development tax credit carryforwards are available indefinitely. Our 2023 current tax expense includes a benefit of approximately $3.2 million related to utilization of state tax loss carryforwards, primarily California.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;56,567&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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 lapse of statute of limitations&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;(14,993&lt;/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;&#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: 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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(737&lt;/div&gt;
        &lt;/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;(267&lt;/div&gt;
        &lt;/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;(695&lt;/div&gt;
        &lt;/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;Increase 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;429&lt;/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;259&lt;/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;263&lt;/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;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; 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;2,032&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;1,490&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;1,354&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;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;" 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;43,298&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;56,567&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;55,085&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;Included in the balance of unrecognized tax benefits at December 31, 2023, 2022 and 2021 was $0.3 million, $6.2 million and $6.2 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 $7.6 million within the next 12 months due to the lapse of statute of limitations on underlying tax positions primarily related to amortization of certain
    capitalized state research and development expenditures.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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, 2023, 2022 and 2021, we recognized $0.1 million, $0.8 million and $0.5 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are subject to taxation in the U.S. and various state and
      foreign jurisdictions. U.S. tax years 2020 through 2022 remain open to examination and tax years 2019 through 2022 remain open to examination by major state taxing jurisdictions, primarily California, although net operating loss and credit
      carryforwards generated prior to these periods 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;/span&gt;.&lt;/div&gt;
</us-gaap:IncomeTaxDisclosureTextBlock>
    <us-gaap:ScheduleOfIncomeBeforeIncomeTaxDomesticAndForeignTableTextBlock
      contextRef="c20230101to20231231"
      id="Text_7281bd0eb54443b994694c659a6a8f66">
&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;"&gt;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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;(334,707&lt;/div&gt;
        &lt;/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;(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;/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;742&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;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;/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;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;(333,965&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;(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;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfIncomeBeforeIncomeTaxDomesticAndForeignTableTextBlock>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_1154d9477ea5403c89bcaba61b591e79"
      unitRef="U001">-334707000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_74d3abad4f744e0aa68801acc3a6ed6b"
      unitRef="U001">-258493000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic
      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_8977ca2c8272434794efd8259c5f22b7"
      unitRef="U001">-29966000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_70ca994a31be49619caefe5e71de1587"
      unitRef="U001">742000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_8425f2adaf6948cdb4db61cdf7def1fc"
      unitRef="U001">508000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_15eeca6092a14a5c9b839eb716ea8ae4"
      unitRef="U001">818000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_317564d38d3f4684aaa47f65a5d386e8"
      unitRef="U001">-333965000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_9fd05fd89e164623ad7d51c758cf30c6"
      unitRef="U001">-257985000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest
      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_225bd758b4d047a9b56b2a1266e8768e"
      unitRef="U001">-29148000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest>
    <us-gaap:ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock
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      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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;" 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;35,861&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;(3,687&lt;/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;1,129&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;/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;147&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;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;/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;32,321&lt;/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;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;/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;&#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%; 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;&#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: -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;32,321&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;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;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock>
    <us-gaap:CurrentFederalTaxExpenseBenefit
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_f7d1c022ad9f48ddaa94094db5e10a09"
      unitRef="U001">35861000</us-gaap:CurrentFederalTaxExpenseBenefit>
    <us-gaap:CurrentFederalTaxExpenseBenefit
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_3b8dd023e1f647b8a3ac8d6daa73c20c"
      unitRef="U001">10522000</us-gaap:CurrentFederalTaxExpenseBenefit>
    <us-gaap:CurrentFederalTaxExpenseBenefit
      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_7390edee7ebc486d8f38622d5c52bcc1"
      unitRef="U001">-200000</us-gaap:CurrentFederalTaxExpenseBenefit>
    <us-gaap:CurrentStateAndLocalTaxExpenseBenefit
      contextRef="c20230101to20231231"
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      id="Fact_29cdf46cccf847508b045e7ee750b157"
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    <us-gaap:CurrentStateAndLocalTaxExpenseBenefit
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_18598915ff304ad69c4f603530fa17ba"
      unitRef="U001">1129000</us-gaap:CurrentStateAndLocalTaxExpenseBenefit>
    <us-gaap:CurrentStateAndLocalTaxExpenseBenefit
      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_b16b487bd08b4f16b0833b9f760c9124"
      unitRef="U001">-690000</us-gaap:CurrentStateAndLocalTaxExpenseBenefit>
    <us-gaap:CurrentForeignTaxExpenseBenefit
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_ca5d84cba52a406991333d46438a92be"
      unitRef="U001">147000</us-gaap:CurrentForeignTaxExpenseBenefit>
    <us-gaap:CurrentForeignTaxExpenseBenefit
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_7ac2061535c24653b193dc9c25179163"
      unitRef="U001">86000</us-gaap:CurrentForeignTaxExpenseBenefit>
    <us-gaap:CurrentForeignTaxExpenseBenefit
      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_94c31631758a4c52bc819107405e16bf"
      unitRef="U001">339000</us-gaap:CurrentForeignTaxExpenseBenefit>
    <us-gaap:CurrentIncomeTaxExpenseBenefit
      contextRef="c20230101to20231231"
      decimals="-3"
      id="Fact_273269185dee42eb91195045f6449fc7"
      unitRef="U001">32321000</us-gaap:CurrentIncomeTaxExpenseBenefit>
    <us-gaap:CurrentIncomeTaxExpenseBenefit
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_33a16e765b9c499ba27c595254ef3547"
      unitRef="U001">11737000</us-gaap:CurrentIncomeTaxExpenseBenefit>
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      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_2d44830595d442f082fda176f5b4c723"
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      id="Fact_87cec1e54272412b8aa84293213da2a9"
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      contextRef="c20220101to20221231"
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      id="Fact_3fdf75baf2f34ebb8e8ae479ea28b0dc"
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      contextRef="c20220101to20221231"
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      id="Fact_b02665644bb848b5b79ed1b9b7aba937"
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    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20230101to20231231"
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      id="Fact_39aa3556afa54b90a94840a97eb5b995"
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    <us-gaap:IncomeTaxExpenseBenefit
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_d3a17d5cbd604f2eaffbec171dab238a"
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      contextRef="c20210101to20211231"
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      id="Fact_72e6d39ff1da4d90b52e886f5e5ff672"
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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;"&gt;Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to loss before income 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;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;/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 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;(333,965&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;(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;/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;(70,133&lt;/div&gt;
        &lt;/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;(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;/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;(22,597&lt;/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;6.8&lt;/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;(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;/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;(22&lt;/div&gt;
        &lt;/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;(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;/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;175,388&lt;/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;(52.5&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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;/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;&#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;/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;(67,131&lt;/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;20.1&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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;/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;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;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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;(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;/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;1,023&lt;/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;(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;/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;3,814&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(1.1&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;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;/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;327&lt;/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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;/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;Foreign-derived intangible income benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,493&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;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.2&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;&#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;&#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; 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;19,546&lt;/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;(5.9&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;14,030&lt;/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;(5.4&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;4,720&lt;/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;(16.2&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;/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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(405&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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" 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%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0); white-space: nowrap;" 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: 4px double rgb(0, 0, 0);" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, 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: 4px double rgb(0, 0, 0);" valign="bottom"&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, 2023 and 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; 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/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;77,964&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;239,962&lt;/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;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;/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;71,683&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;77,468&lt;/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;86,983&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;/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;104,380&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;104,649&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;/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;16,849&lt;/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;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;/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;Capitalized research and development 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;238,738&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;119,635&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;Long-term 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;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;43,718&lt;/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;45,612&lt;/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; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Sale of future royalties&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;144,608&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;10,343&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;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;/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;1,025,713&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;(4,166&lt;/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;(4,475&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;/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;(42,007&lt;/div&gt;
        &lt;/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;(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;/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;(1,910&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;(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;/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;977,630&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;(977,630&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;(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;/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;

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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="display:none;"&gt;&lt;br/&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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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; 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;56,567&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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 lapse of statute of limitations&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;(14,993&lt;/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;&#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: 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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(737&lt;/div&gt;
        &lt;/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;(267&lt;/div&gt;
        &lt;/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;(695&lt;/div&gt;
        &lt;/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;Increase 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;429&lt;/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;259&lt;/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;263&lt;/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;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; 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;2,032&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;1,490&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;1,354&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;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;" 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;43,298&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;56,567&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;55,085&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:ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock>
    <us-gaap:UnrecognizedTaxBenefits
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      unitRef="U001">56567000</us-gaap:UnrecognizedTaxBenefits>
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      decimals="-3"
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      unitRef="U001">737000</us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions>
    <us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions
      contextRef="c20220101to20221231"
      decimals="-3"
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      unitRef="U001">267000</us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions>
    <us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions
      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_0bb19795798b4cca8d22978a26340bd0"
      unitRef="U001">695000</us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions>
    <us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions
      contextRef="c20230101to20231231"
      decimals="-3"
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      unitRef="U001">429000</us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions>
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      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_0ad407c0955648c48850ba2d8d052462"
      unitRef="U001">259000</us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions>
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      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_7d0ea3f6a325421b85ab3cbb04eb12fa"
      unitRef="U001">263000</us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions>
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      contextRef="c20230101to20231231"
      decimals="-3"
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      unitRef="U001">2032000</us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions>
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      contextRef="c20220101to20221231"
      decimals="-3"
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      unitRef="U001">1490000</us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions>
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      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_809af95107674a60b9a6aa50165e5ba7"
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      id="Fact_ed1574437d194d92b955e24fdec9efce"
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      id="Fact_552285171ef248dfab36d0ee9948271e"
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      contextRef="c20221231"
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      id="Fact_609bbfafde0b4ea9bce0bad6399c9eb6"
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      contextRef="c20211231"
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      id="Fact_49d7f6eb2570409abc1312c432abdfe0"
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      decimals="-5"
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      decimals="-5"
      id="Fact_8781f6db0d834e54aff079e85ee20d63"
      unitRef="U001">500000</us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense>
    <us-gaap:PensionAndOtherPostretirementBenefitsDisclosureTextBlock
      contextRef="c20230101to20231231"
      id="Text_44a1974bfba9485682c02d2913778f03">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;10. 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 $22,500 and $30,000 in 2023 for employees under 50 years old and employees 50 years old or over,
    respectively. We made approximately $7.1 million, $5.6
    million and $5.5 million in matching contributions for the years ended December 31, 2023, 2022 and 2021, respectively.&lt;/div&gt;
</us-gaap:PensionAndOtherPostretirementBenefitsDisclosureTextBlock>
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      id="Fact_06c142c7ec1040e0b05c4b2596dfe112"
      unitRef="U001">22500</us-gaap:DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount>
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      contextRef="c20230101to20231231_RangeAxis_MaximumMember"
      decimals="0"
      id="Fact_2703ad6213db4e249c38d0794a2c6418"
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    <us-gaap:DefinedContributionPlanCostRecognized
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    <us-gaap:LegalMattersAndContingenciesTextBlock
      contextRef="c20230101to20231231"
      id="Text_656730b2a28e4e958b751e639ff66fd5">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;11. 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;There are no pending material legal proceedings to which we are a party or of which our property is the subject.&lt;/div&gt;
</us-gaap:LegalMattersAndContingenciesTextBlock>
    <us-gaap:QuarterlyFinancialInformationTextBlock
      contextRef="c20230101to20231231"
      id="Text_4be6328593df49c295c60f8f5c9d4bc0">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;12. 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 2023 and 2022 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/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;324,505&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;330,627&lt;/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;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;/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;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;(6,122&lt;/div&gt;
        &lt;/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;(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;/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 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;(9,263&lt;/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;(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;/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 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;(0.06&lt;/div&gt;
        &lt;/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;(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;/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 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;(0.06&lt;/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;(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;/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 higher in the three months ended December 31, 2023
            compared to the same period in 2022 primarily due to the $50 million milestone payment we earned from AstraZeneca when the FDA approved
            WAINUA for ATTRv-PN in the U.S., $36 million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth
            quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis.&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 lower in the three months ended December 31,
            2023 compared to the same period in 2022 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 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 loss per share by dividing the total net 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 incurred a net loss for the fourth quarter of 2023 and 2022. As a
            result, 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.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:QuarterlyFinancialInformationTextBlock>
    <us-gaap:ScheduleOfQuarterlyFinancialInformationTableTextBlock
      contextRef="c20230101to20231231"
      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 2023 and 2022 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;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;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;/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;324,505&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/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;330,627&lt;/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;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;/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;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;(6,122&lt;/div&gt;
        &lt;/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;(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;/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 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;(9,263&lt;/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;(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;/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 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;(0.06&lt;/div&gt;
        &lt;/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;(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;/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 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;(0.06&lt;/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;(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;/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 higher in the three months ended December 31, 2023
            compared to the same period in 2022 primarily due to the $50 million milestone payment we earned from AstraZeneca when the FDA approved
            WAINUA for ATTRv-PN in the U.S., $36 million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth
            quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis.&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 lower in the three months ended December 31,
            2023 compared to the same period in 2022 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 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 loss per share by dividing the total net 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 incurred a net loss for the fourth quarter of 2023 and 2022. As a
            result, 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.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfQuarterlyFinancialInformationTableTextBlock>
    <us-gaap:Revenues
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      id="Fact_284eab838adc45f1bab65fa3ed3e8a21"
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    <us-gaap:Revenues
      contextRef="c20221001to20221231"
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      id="Fact_20e60632220f4799962c4c0ff5f00ab5"
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    <us-gaap:CostsAndExpenses
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      id="Fact_ef4a183f40c64bdd8dd30738366a5262"
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      id="Fact_c3c0e5d7387e40eb92385001e70edef5"
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      id="Fact_af25cdfae24542caac610d75303df0eb"
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    <us-gaap:EarningsPerShareBasic
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    <us-gaap:EarningsPerShareBasic
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    <us-gaap:EarningsPerShareDiluted
      contextRef="c20231001to20231231"
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      id="Fact_a89ed465fb1d45109c8bb5281937ec8f"
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    <us-gaap:EarningsPerShareDiluted
      contextRef="c20221001to20221231"
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      id="Fact_50ffd0d9a803420490859b8fc30d4b07"
      unitRef="U004">-0.37</us-gaap:EarningsPerShareDiluted>
    <us-gaap:Revenues
      contextRef="c20231001to20231231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember"
      decimals="-6"
      id="Fact_75e24768ba824a2b9a04b8c91d513855"
      unitRef="U001">50000000</us-gaap:Revenues>
    <us-gaap:Revenues
      contextRef="c20231001to20231231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember"
      decimals="-6"
      id="Fact_14c3c8ccfb6f458f890a035fb5e35122"
      unitRef="U001">36000000</us-gaap:Revenues>
    <us-gaap:ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost
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      unitRef="U001">80000000</us-gaap:ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost>
    <us-gaap:SaleAndLeasebackTransactionGainLossNet
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      decimals="-5"
      id="Fact_93d3cf8aaae24601bac724efc7d56b2b"
      unitRef="U001">150100000</us-gaap:SaleAndLeasebackTransactionGainLossNet>
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        <link:footnote id="Foot_bcf863dbf8484660b7f8b1e68ba84eea" xlink:label="Foot_bcf863dbf8484660b7f8b1e68ba84eea" xlink:role="http://www.xbrl.org/2003/role/footnote" xlink:type="resource" xml:lang="en-US"><xhtml:span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </xhtml:span>compute net loss per share independently for each quarter during <xhtml:span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</xhtml:span></link:footnote>
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